Global Behavior of a Discrete Survival Model with Several Delays

The difference equation yn+1−yn=−αyn+∑j=1mβje−γjyn−kj is studied and some sufficient conditions which guarantee that all solutions of the equation are oscillatory, or that the positive equilibrium of the equation is globally asymptotically stable, are obtained

Experimental investigation on plugging performance of nanospheres in low-permeability reservoir with bottom water

The oil production rate decreases rapidly after a short period of high yield from acidizing or fracturing in low-permeability reservoirs. In this paper, nanospheres are applied before the fracturing step, which possess the ability to absorb water and expand in the water layer, reducing the flow capacity of bottom water and finally enhancing the oil recovery. The plugging performance is investigated by nanosphere displacement  experiments in cores and sand-packs, which explores the plugging effect in the oil layer, the oil-water transition zones, the water layer and the fracturing zones. In addition, a nuclear magnetic resonance experiment is conducted to study the flow mechanism of nanospheres and determine the plugging rates, which can characterize the plugging performance of nanospheres in porous media. The results show that the plugging rate is 85.84% and 78.65% on the water layer and oil-water transition zone, respectively, and 94.36% in the fracturing zone. Meanwhile, the nanospheres cannot plug the oil layer. The formation pressure has a less considerable effect on the plugging performance of nanospheres. The nanospheres have good injectivity, and the intensity variations in small, medium and large pores account for 34.46%, 13.22% and 52.32%, respectively. Overall, this paper explores the feasibility of applying nanospheres for water plugging and enhanced oil recovery.Cited as: Tang, M., Wang, C., Deng, X., Yang, H., Lu, J., Yu, H. Experimental investigation on plugging performance of nanospheres in low-permeability reservoir with bottom water. Advances in Geo-Energy Research, 2022, 6(2): 95-103. https://doi.org/10.46690/ager.2022.02.0

Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.

Collagen is the most abundant protein in animals. Its dysregulation contributes to aging and many human disorders, including pathological tissue fibrosis in major organs. How premature collagen proteins in the endoplasmic reticulum (ER) assemble and route for secretion remains molecularly undefined. From an RNA interference screen, we identified an uncharacterized Caenorhabditis elegans gene tmem-131, deficiency of which impairs collagen production and activates ER stress response. We find that amino termini of human TMEM131 contain bacterial PapD chaperone-like domains, which recruit premature collagen monomers for proper assembly and secretion. Carboxy termini of TMEM131 interact with TRAPPC8, a component of the TRAPP tethering complex, to drive collagen cargo trafficking from ER to the Golgi. We provide evidence that previously undescribed roles of TMEM131 in collagen recruitment and secretion are evolutionarily conserved in C. elegans, Drosophila, and humans

Tumor-targeted delivery of sunitinib base enhances vaccine therapy for advanced melanoma by remodeling the tumor microenvironment

Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. We have previously developed a potent mannose-modified lipid calcium phosphate (LCP) nanoparticle (NP)-based Trp2 vaccine for melanoma therapy, but because this vaccine can induce a potent anti-tumor immune response only during the early stages of melanoma, poor tumor growth inhibition has been observed in more advanced melanoma models, likely due to the development of an immune-suppressive tumor microenvironment (TME). To effectively treat this aggressive tumor, a multi-target receptor tyrosine kinase inhibitor, sunitinib base, was efficiently encapsulated into a targeted polymeric micelle nano-delivery system (SUNb-PM), working in a synergistic manner with vaccine therapy in an advanced mouse melanoma model. SUNb-PM not only increased cytotoxic T-cell infiltration and decreased the number and percentage of MDSCs and Tregs in the TME, but also induced a shift in cytokine expression from Th2 to Th1 type while remodeling the tumor-associated fibroblasts, collagen, and blood vessels in the tumor. Additionally, inhibition of the Stat3 and AKT signaling pathways by SUNb-PM may induce tumor cell apoptosis or decrease tumor immune evasion. Our findings indicated that targeted delivery of a tyrosine kinase inhibitor to tumors can be used in a novel synergistic way to enhance the therapeutic efficacy of existing immune-based therapies for advanced melanoma

Diabetes-associated neutrophil NETosis: pathogenesis and interventional target of diabetic complications

Neutrophil extracellular traps (NETs) are known as extracellular fibers networks consisting of antimicrobial proteins and decondensated chromatin DNA released by activated neutrophils. NETosis is a NETs-induced neutrophilic cell death which is unique from necrosis or apoptosis. Besides its neutralizing pathogen, NETosis plays a crucial role in diabetes and diabetes-related complications. In patients with diabetes, NETs-releasing products are significantly elevated in blood, and these findings confirm the association of NETosis and diabetic complications, including diabetic wound healing, diabetic retinopathy, and atherosclerosis. This article briefly summarizes the mechanisms of NETosis and discusses its contribution to the pathogenesis of diabetes-related complications and suggests new therapeutic targets by some small molecule compounds

Direct production of dihydroxylated sesquiterpenoids by a maize terpene synthase

The astounding structural and biological diversity of the large class of terpenoid natural products are imparted by both their complex hydrocarbon backbones and further elaboration by the addition of multiple hydroxyl groups, which provide both solubility and specific binding properties. While the role of terpene synthases in generating hydrocarbons with complex backbones is well known, these also are known to generate (singly) hydroxylated products by the addition of water prior to terminating deprotonation. Here a maize sesquiterpene synthase was unexpectedly found to generate dually hydroxylated products directly from (E,E)-farnesyl diphosphate, primarily eudesmane-2,11-diol, along with two closely related structural isomers. The unprecedented formation of these diols was proposed to proceed via initial addition of water to a germacradienyl+ intermediate, followed by protonation of the internal carbon-6,7-double-bond in the resulting hedycarol, with subsequent cyclization and further addition of water to an eudesmolyl+ intermediate. Evidence for the proposed mechanism was provided by labeling studies, as well as site-directed mutagenesis, based on structural modeling, which identified an active site phenylalanine required for the protonation and further elaboration of hedycaryol. This di-hydroxylated sesquiterpenoid synthase was specifically expressed in maize roots and induced by pathogen infection, with its major enzymatic product only detected in root exudates or infected roots, suggesting a role in defense. Regardless of the ultimate metabolic fate or physiological role of these diols, this report not only reveals an unanticipated extension of the catalytic prowess of terpene synthases, but also provides insight into the underlying enzymatic mechanism