Nicotinamide adenine dinucleotide (NAD+) is an essential biomolecule involved in many critical processes. Its role as both a driver of energy production and a signaling molecule underscores its ...importance in health and disease. NAD+ signaling impacts multiple processes that are dysregulated in cancer, including DNA repair, cell proliferation, differentiation, redox regulation, and oxidative stress. Distribution of NAD+ is highly compartmentalized, with each subcellular NAD+ pool differentially regulated and preferentially involved in distinct NAD+-dependent signaling or metabolic events. Emerging evidence suggests that targeting NAD+ metabolism is likely to repress many specific mechanisms underlying tumor development and progression, including proliferation, survival, metabolic adaptations, invasive capabilities, heterotypic interactions with the tumor microenvironment, and stress response including notably DNA maintenance and repair. Here we provide a comprehensive overview of how compartmentalized NAD+ metabolism in mitochondria, nucleus, cytosol, and extracellular space impacts cancer formation and progression, along with a discussion of the therapeutic potential of NAD+-targeting drugs in cancer.
According to modern cosmology, expansion of the universe is due to the metric changing of spacetime itself. Here, we propose to mimic an expanding universe by utilizing optical interference and ...helicoid waveguides. The evolution of interference pattern in the helicoid waveguide is investigated theoretically and experimentally. For precise measurements, we design an air helicoid waveguide which allows us to investigate the wave front of laser beams from the waveguide. Redshift of a Gaussian wave packet in the expanding universe is demonstrated with high precision, showing that the helicoid waveguide acts as a parabolic gradient index lens exactly. The proposed waveguide structure can be used as an efficient waveguide adapter.
The objective of the study was to investigate the mechanism by which arginine regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d-old male Pekin ducks were randomly ...allotted to 3 dietary treatments with 6 replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P < 0.05) than the other 2 groups. In experiment 2, twenty 11-d-old ducks were allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl (L-NAME) for 3 d, respectively. Feed intake (P < 0.07) and plasma nitric oxide concentration (P < 0.05) 2 h postinjection in the L-NAME administered group were lower than those of the control group. In conclusion, the study implied that arginine modifies feeding behavior possibly through controlling endogenous synthesis of nitric oxide in Pekin ducks.
Now, lodging is a major constraint factor contributing to yield loss of maize (Zea mays L.) under high planting density. Chemical regulation and nitrogen fertilizer could effectively coordinate the ...relationship between stem lodging and maize yield, which significantly reduce lodging and improve the grain yield. The purpose of this study was to explore the effects of chemical regulation and different nitrogen application rates on lodging characteristics, grain filling and yield of maize under high density. For this, we established a field study during 2017 and 2018 growing seasons, with three nitrogen levels of N100 (100 kg ha–1), N200 (200 kg ha–1) and N300 (300 kg ha–1) at high planting density (90 000 plants ha–1), and applied plant growth regulator (Yuhuangjin, the mixture of 3% DTA-6 and 27% ethephon) at the 7th leaf. The results showed that chemical control increased the activities of phenylalanine ammonia-lyase (PAL), tyrosine ammonia-lyase (TAL), 4-coumarate:CoA ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD), and increased the lignin, cellulose and hemicellulose contents at the bottom of the 3rd internode, which significantly reduced the lodging percentage. The lignin-related enzyme activities, lignin, cellulose and hemicellulose contents decreased with the increase of nitrogen fertilizer, which significantly increased the lodging percentage. The 200 kg ha–1 nitrogen application and chemical control increased the number, diameter, angle, volume, and dry weight of brace roots. The 200 kg ha–1 nitrogen application and chemical control significantly increased the activities of ADP-glucose pyrophosphorylase (AGPase), soluble starch synthase (SSS) and starch branching enzyme (SBE), which promoted the starch accumulation in grains. Additional, improved the maximum grain filling rate (Vmax) and mean grain filling rate (Vm), which promoted the grain filling process, significantly increased grain weight and grain number per ear, thus increased the final yield.
Summary
The phagocytic clearance of apoptotic cells is critical for tissue homeostasis; a number of non‐professional phagocytic cells, including epithelial cells, can both take up and process ...apoptotic bodies, including the release of anti‐inflammatory mediators. These observations are particularly important in the case of human intrahepatic biliary cells (HiBEC), because such cells are themselves a target of destruction in primary biliary cirrhosis, the human autoimmune disease. To address the apoptotic ability of HiBECs, we have focused on their ability to phagocytize apoptotic blebs from autologous HiBECs. In this study we report that HiBEC cells demonstrate phagocytic function from autologous HiBEC peers accompanied by up‐regulation of the chemokines CCL2 monocyte chemotactic protein‐1 (MCP‐1) and CXCL8 interleukin (IL)‐8. In particular, HiBEC cells express the phagocytosis‐related receptor phosphatidylserine receptors (PSR), implying that HiBECs function through the ‘eat‐me’ signal phosphatidylserine expressed by apoptotic cells. Indeed, although HiBEC cells acquire antigen‐presenting cell (APC) function, they do not change the expression of classic APC function surface markers after engulfment of blebs, both with and without the presence of Toll‐like receptor (TLR) stimulation. These results are important not only for understanding of the normal physiological function of HiBECs, but also explain the inflammatory potential and reduced clearance of HiBEC cells following the inflammatory cascade in primary biliary cirrhosis.
Symbiotic relationships are ubiquitous in the biosphere. Inter-species symbiosis is impacted by intra-specific distinctions, in particular, those defined by the age structure of a population. Older ...individuals compete with younger individuals for resources despite being less likely to reproduce, diminishing the fitness of the population. Conversely, however, older individuals can support the reproduction of younger individuals, increasing the population fitness. Parasitic relationships are commonly age structured, typically, more adversely affecting older hosts. We employ mathematical modeling to explore the differential effects of collaborative or competitive host age structures on host-parasite relationships. A classical epidemiological compartment model is constructed with three disease states: susceptible, infected, and recovered. Each of these three states is partitioned into two compartments representing young, potentially reproductive, and old, post-reproductive, hosts, yielding 6 compartments in total. In order to describe competition and collaboration between old and young compartments, we model the reproductive success to depend on the fraction of young individuals in the population. Collaborative populations with relatively greater numbers of post-reproductive hosts enjoy greater reproductive success whereas in purely competitive populations, increasing the post-reproductive subpopulation reduces reproductive success. We demonstrate that, in collaborative host populations, pathogens strictly impacting older, post-reproductive individuals can reduce population fitness even more than pathogens that directly impact younger, potentially reproductive individuals. In purely competitive populations, the reverse is observed, and we demonstrate that endemic, virulent pathogens can oxymoronically form a mutualistic relationship with the host, increasing the fitness of the host population. Applications to endangered species conservation and invasive species containment are discussed.
The goal of this research is to study the dynamic properties and fracture damage laws of granite at the meso-scale under impact load. The quasi-static and dynamic mechanical properties of granite ...were studied through laboratory tests (Uniaxial compression, split Hopkinson pressure bar). The establishment of three-dimensional coupled numerical model of rock specimen and split Hopkinson pressure bar was realized by new coupling technology of PFC-FLAC. Three wave superposition and end stress distribution were discussed to determine the stress balance of the specimen during the loading process. The dynamic compression mechanics response characteristics and crack growth laws of granite under different strain rates were studied. The results indicated that PFC-FLAC coupling technology can solve the problems of tedious modeling process and long calculation time in the past three-dimensional discrete element model, and can better describe the dynamic mechanical behaviour of rock. There is obvious rate dependency in the dynamic strength of rock material, and the dynamic compressive strength of rock increases with the increase of strain rate. The macro fracture of rock mass is the result of the continuous development, expansion, aggregation and connection of the internal microcracks. With the increase of strain rate, the increase and cross propagation of cracks lead transformation of rock from intact to crushing destruction. Under dynamic loading, the failure process of rock is crack initiation, propagation, crossing, transfixion and rupture.
Summary
Primary biliary cirrhosis (PBC) is an organ‐specific autoimmune liver disease characterized by progressive loss of intrahepatic small bile ducts. Cellular immune mechanisms involving T cell ...reaction are thought to be involved significantly in the pathogenesis of PBC. Recent studies have independently revealed enhanced T helper type 17 (Th17) response and weakened T regulatory cell (Treg) response in some autoimmune diseases, indicating a role of Th17/Treg imbalance in the pathogenesis of autoimmunity. This prompted us to investigate whether the Th17/Treg balance was broken in the peripheral blood of patients with PBC and, if it was, what cytokine circumstances might contribute to this imbalance. The expression of 11 Th17/Treg differentiation‐related genes and serum concentrations of the corresponding cytokines in 36 patients with PBC, 28 patients with chronic hepatitis B and 28 healthy controls were measured by real‐time quantitative–polymerase chain reaction and enzyme‐linked immunosorbent assay respectively. Peripheral Th17 and Treg cells were analysed by flow cytometry. Th17‐related cytokines were increased significantly in patients with PBC. Consistent with the cytokine profile, the Th17 cell population and retinoid‐related orphan receptor γt expression were increased markedly. In contrast, the Treg cell population and forkhead box P3 expression were decreased dramatically in the peripheral blood of patients with PBC. Our study revealed that the Th17/Treg imbalance, both cytokine profile and cell numbers, exists in patients with PBC, suggesting its potential role in the breakdown of immune self‐tolerance in PBC. Interleukin‐23, which characterized the imbalanced cytokine profile, may play an essential role in Th17‐related human autoimmunity.
Twenty-six avian infectious bronchitis (IB) viruses (IBV) were isolated from outbreaks in chickens in China between 1995 and 2004. They were characterized by comparison with twenty-six Chinese ...reference strains and five other IBV strains. Chinese IBVs, which were mainly nephropathogenic, were placed into seven genotypes. Fourteen Chinese IBV isolates were placed in genotype I, having small evolutionary distances from each other. Genotype II included 6 strains that were isolated in the 1990s in China. Genotype III consisted of eight Chinese isolates that showed close relationship with Korean IBV isolates. Another eight IBV isolates clustered in genotype IV and showed larger evolutionary distances. The Massachusetts serotype was present in China in 1990s and was in a separate genotype. Two isolates, HN99 and CK/CH/LHN/00I, which might be a reisolation of vaccine strains, clustered into genotype VI. Four Chinese IBV isolates formed another genotype and showed larger evolutionary distances from other Chinese IBV genotypes (genotype VII). IBVs in same genotypes showed more than 90% amino acid sequence similarities, whereas most of the viruses in different genotypes showed less than 90%. The results showed that IBVs in China came from genetic changes both in IBV populations that existed before the advent of vaccination and in the viruses that were introduced through live vaccines. IBVs showing various genetic differences are cocirculating in China.
By globally analyzing all existing measured branching fractions for D→πe+νe decays, partial decay rates in different four-momentum transfer-squared q2 bins, as well as products of the decay form ...factor f+π(q2) and the Cabibbo–Kobayashi–Maskawa (CKM) quark-mixing matrix element |Vcd|, we obtain f+π(0)|Vcd|=0.1428±0.0019−0.0011+0.0019. This product, in conjunction with the |Vus| determined from (semi-)leptonic K decays and the relation of |Vcd|=|Vus|=λ from the unitarity of the CKM matrix, implies a value for the D→π semileptonic form factor f+π(0)=0.634−0.010+0.012±0.002, which is consistent within error with those calculated in theory based on quantum chromodynamics (QCD). Alternately, using this product together with the most accurate form factor calculated in Lattice QCD (LQCD), we find |Vcd|D→πe+νe=0.2144−0.0033+0.0040±0.0093. Combining this |Vcd|D→πe+νe with |Vcd|D+→μ+νμ=0.2160±0.0049±0.0014 extracted from both the BESIII and CLEO-c measurements of D+→μ+νμ decays, we find the most precisely extracted |Vcd| to be |Vcd|=0.2157±0.0045 up to date. From these determined quantities we find mD+f+π(0)/fD+exp=5.81±0.17, which is in excellent agreement with mD+f+π(0)/fD+LQCD=5.85±0.26 calculated in LQCD, indicating that the LQCD approach to the charm quark sector is excellent. Using this |Vcd| together with the PDG'2014 |Vud| and |Vtd|, we check for the first column unitarity and find |Vud|2+|Vcd|2+|Vtd|2−1=−0.004±0.002, which deviates from unitarity by 2σ.
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