Although quinone production and melanin formation are widely recognized as an integral part of the insect defense system, experimental evidence is lacking that the proteolytic activation of prophenoloxidase participates in the direct killing of invading microbes-active phenoloxidase generates quinones that polymerize to form melanin. Here, we report the antimicrobial effect of reactive intermediates produced in phenoloxidase-catalyzed reactions. After being treated with Manduca sexta phenoloxidase and dopamine, Escherichia coli and Bacillus subtilis ceased to grow, whereas the growth of Pichia pastoris was slightly affected. Microscopic analysis showed melanin deposition on cell surface, aggregation of bacteria, and loss of cell mobility. Viability tests revealed major decreases in the bacterial colony counts and, since the decrease remained significant after dispersion of the cell clumps, the reactive compounds were surmised to have aggregated and killed E. coli and B. subtilis cells. Under the experimental conditions, 60-94% of the Gram-negative bacteria (E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella typhimurium) and 52-99% of the Gram-positive bacteria (Bacillus cereus, B. subtilis, Micrococcus luteus, and Staphylococcus aureus) were killed. In the presence of phenoloxidase, dopamine or 5,6-dihydroxyindole (DHI) exhibited much higher antibacterial activity than L-dopa, N-acetyldopamine (NADA) or N-β-alanyldopamine (NBAD) did, suggesting that DHI and its oxidation products were cytotoxic. The antifungal activity of DHI was detected using P. pastoris, Saccharomyces cerevisiae, Candida albicans, and Beauveria bassiana. These results established that prophenoloxidase activation is an integral component of the insect defense system involving a multitude of enzymes (e.g. proteinases, oxidases, and dopachrome conversion enzyme (DCE)), which immobilizes and kills invading microorganisms.

Polyamines are aliphatic compounds with more than two amino groups that play various important roles in human cells. In cancer, polyamine metabolism dysfunction often occurs, and regulatory mechanisms of polyamine. This review summarizes the existing research on the metabolism and transport of polyamines to study the association of oncogenes and related signaling pathways with polyamines in tumor cells. Drugs that regulate enzymes have been developed for cancer treatment, and in the future, more attention should be paid to treatment strategies that simultaneously modulate polyamine metabolism and carcinogenic signaling pathways. In addition, the polyamine pathway is a potential target for cancer chemoprevention. As an irreversible suicide inhibitor of the ornithine decarboxylase (a vital enzyme of polyamine synthesis), Difluoro-methylornithine had been shown to have the chemoprevention effect on cancer. Therefore, we summarized and analyzed the chemoprophylaxis effect of the difluoromethylornithine in this systematic review.

Temperature sensors with micro- and nanoscale spatial resolution have long been explored for their potential to investigate the details of physical systems at an unprecedented scale. In particular, the rapid miniaturization of transistor technology, with its associated steep boost in power density, calls for sensors that accurately monitor heating distributions. Here, we report on a simple and scalable fabrication approach, based on directed self-assembly and transfer-printing techniques, to constructing arrays of nanodiamonds containing temperature-sensitive fluorescent spin defects. The nanoparticles are embedded within a low-thermal-conductivity matrix that allows for repeated use on a wide range of systems with minimal spurious effects. Additionally, we demonstrate access to a wide spectrum of array parameters ranging from sparser single-particle arrays, with the potential for quantum computing applications, to denser devices with 98 ± 0.8% yield and stronger photoluminescence signals, ideal for temperature measurements. With these, we experimentally reconstruct the temperature map of an operating coplanar waveguide to confirm the accuracy of these platforms.

BackgroundThe alarming progression of an increasingly aging population in China has attracted much attention within the country and abroad. In 2003, the Chinese central government launched the New Cooperative Medical Scheme (NCMS) to resolve problems of healthcare inequity in regions with inadequate infrastructure and relative poverty. The purpose of this study was to investigate the effect of NCMS on health expenditures by the Chinese rural elderly population.MethodsThe data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which was conducted in 2005, 2008, 2011 and 2014. Elderly people living in rural areas and 60 years old or above were screened for the investigation. The sample size was 7472 in 2005, 11,705 in 2008, 9239 in 2011, and 6059 in 2014. The OOP% and reimbursement ratio were the medical expenses paid by individuals accounting for their per capita annual income and the medical expenses paid by medical insurance accounting for their total medical expenses, respectively. By controlling for individuals’ sociodemographic characteristics, pensions, demands and utilization of health services, we estimated the effect of the NCMS on the OOP% and reimbursement ratio for the rural elderly using seemingly unrelated regression (SUR).ResultsThe NCMS coverage ranged from 11.63% in 2005 to 80.34% in 2014. The medical expenses of the elderly also increased from an average of $204.77 in 2005 to $696.23 in 2014, which was more than three times as much as in 2005. From 2005 to 2014, the reimbursement ratio for medical expenses of rural elderly people with NCMS increased significantly from 30.6% in 2005 to 56.1% in 2014. The proportion of reimbursement ratio for rural seniors with NCMS increased by 6.4% across each survey cycle (every 3 years). However, the NCMS resulted in an insignificant decrease in OOP% by 1.4% across each survey cycle (every 3 years). Among other medical insurances, public insurance and private elder insurance had significant positive impacts on reimbursement ratio but did not influence OOP%.ConclusionsNCMS remarkably increased the rural elderly’s reimbursement ratio but insignificantly decreased the rural elderly’s OOP%. In addition, the proportion of reimbursement ratio for NCMS participants increased by 6.4% every 3 years. Lower outpatient reimbursement, migration, limited reimbursement scope, an increasing demand for medical services and the rapid growth of medical expenses may be reasons for the gaps between the nominal reimbursement ratio and the actual reimbursement ratio and OOP%. Policymakers should further modify NCMS policies in rural China.

Nanoparticle assemblies have generated intense interest because of their novel optical, electronic, and magnetic properties that open up numerous opportunities in fundamental and applied nanophotonics, -electronics, and -magnetics. However, despite the great scientific and technological potential of these structures, it remains an outstanding challenge to reliably fabricate such assemblies with both nanometer-level structural control and precise spatial arrangements on a macroscopic scale. It is the combination of these two features that is key to realizing nanoparticle assemblies' potential, particular for device applications. To address this challenge, we propose a hierarchical assembly approach consisting of both template−particle and particle−particle interactions, whereby the former ensures precise addressability of assemblies on a surface and the latter provides nanometer-level structural control. Template−particle interactions are harnessed via chemical-pattern-directed assembly, and the particle−particle interactions are controlled using DNA-directed self-assembly. To demonstrate the potential of this hierarchical assembly approach, we demonstrate the fabrication of a particularly fascinating assembly: the nanoparticle heterodimer, which possesses a surprisingly rich set of plasmonic properties and is a promising candidate to enable a variety of imaging and sensing applications. Each heterodimer is placed on the surface at predetermined locations, and the precise control of the nanogaps is confirmed by far-field scattering measurements of individual dimers. We further demonstrate that the gap size can be effectively tuned by varying the DNA length. By correlating measured spectra with finite-difference time-domain (FDTD) simulations, we determine the gap sizes to be 4.2 and 5.0 nmwith subnm deviationfor the two DNA lengths investigated. This is one of the best gap uniformities ever demonstrated for surface-bound nanoparticle assemblies. The estimated surface-enhanced Raman scattering (SERS) enhancement factor of these heterodimers is on the order of 10 5 −10 6 with high reproducibility and predictable polarizationdependence. This hierarchical fabrication techniqueemploying both template−particle and particle−particle interactions constitutes a novel platform for the realization of functional nanoparticle assemblies on surfaces and thereby creates new opportunities to implement these structures in a variety of applications.

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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world. However, there is still no drug for NAFLD in the market, the study of potential therapeutic drugs on NAFLD is extraordinarily pressing and urgent. The rodent models for NAFLD drugs' study are always with a long time cost. Therefore, we aim to establish a short-time NAFLD drug screening model. A laboratory-made high cholesterol diet was used on larval zebrafish for 3 weeks to establish the NAFLD screen model. Lipid metabolism, oxidant stress, and pathology were studied to comprehensively demonstrate the whole spectrum of NAFLD on this model. Bezafibrate and pioglitazone were used to evaluate the model. Moreover, mechanism research was performed on this model.The NAFLD larval zebrafish model was established with the comprehensive process of NAFLD. Moreover, multiple index on lipid metabolism, oxidant stress, hepatic steatosis, and hepatic inflammation can be easily tested for drug screening. Furthermore, this model can be used to perform the mechanism research by testing mRNA expression. The NAFLD larval zebrafish model is a comprehensive short-time screening method for NAFLD drugs.

Cancer as a large group of complex diseases is believed to result from the interactions of numerous genetic and environmental factors but may develop in people without any known genetic or environmental risks, suggesting the existence of other powerful factors to influence the carcinogenesis process. Much attention has been focused recently on particular members of the intestinal microbiota for their potential roles in promoting carcinogenesis. Here we report the identification and characterization of intestinal bacteria that exhibited potent anti-malignancy activities on a broad range of solid cancers and leukemia. We collected fecal specimens from healthy individuals of different age groups (preschool children and university students), inspected their effects on cancer cells, and obtained bacteria with potent anti-malignancy activities. The bacteria mostly belonged to Actinobacteria but also included lineages of other phyla such as Proteobacteria and Firmicutes. In animal cancer models, sterile culture supernatant from the bacteria highly effectively inhibited tumor growth. Remarkably, intra-tumor administration of the bacterial products prevented metastasis and even cleared cancer cells at remote locations from the tumor site. This work demonstrates the prevalent existence of potent malignancy-killers in the human intestinal microbiota, which may routinely clear malignant cells from the body before they form cancers.