Immunotargeting of collagenase on thrombus

In this study, we aimed to develop a thrombus-targeting delivery system of collagenase bound to a monoclonal antibody, and to investigate the thrombolysis of an immune-conjugate in vitro and in vivo as well as the targeting effect. We prepared the immunizing conjugation of collagenase by the 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDCI) method. In order to conjugate collagenase and a monoclonal antibody, bovine serum albumin was used as a linker, increasing the number of collagenase molecules carried and keeping collagenase and the monoclonal antibody active. In vitro thrombolysis experiments showed that collagenase had a strong dissolving effect on collagen-embolus within 24 hours. We established a rabbit pulmonary embolism model to investigate the thrombolysis effect of collagenase and collagenase immunizing conjugation in vivo. Our results revealed a significant difference between collagenase and collagenase immunizing conjugation (P < 0.05). We also established a rabbit ear edge vein model to investigate the active target of collagenase immunizing conjugation. We found that collagenase immunizing conjugation had active targets, and had a strong ability to dissolve organized thrombi. In conclusion, the thrombus-targeting delivery system of collagenase we developed has active targeting effects on thrombi

Rare appearance of Candida tropicalis infection of the brain: Multiple micro-abscesses combined with diffuse hemorrhages

AbstractWe report a case of cerebral Candida tropicalis infection in a middle-aged patient who suffered from multiple cerebral micro-abscesses associated with diffuse hemorrhage due to perforation of esophagus. MRI revealed multiple irregular, nodular, ring-like enhancing lesions with restricted diffusion and multiple micro-hemorrhages as well as some leptomeningeal enhancements. Blood, sputum and urine cultures showed Candida tropicalis. The lesions were resolved after the patient was given early and effective treatment of anti-fungal medicine. The imaging findings provided limited differential diagnosis, leading to early diagnosis and treatment for this patient

Graphs and Matroids Weighted in a Bounded Incline Algebra

Firstly, for a graph weighted in a bounded incline algebra (or called a dioid), a longest path problem (LPP, for short) is presented, which can be considered the uniform approach to the famous shortest path problem, the widest path problem, and themost reliable path problem. The solutions for LPP and related algorithms are given. Secondly, for a matroid weighted in a linear matroid, the maximum independent set problem is studied

4-[(5-Bromo-2-hy­droxy­benzyl­idene)amino]-3-propyl-1H-1,2,4-triazole-5(4H)-thione

The asymmetric unit of the title compound, C12H13BrN4OS, contains two independent mol­ecules in which the dihedral angles between the triazole and benzene rings are 2.9 (3) and 7.5 (3)°. The thione group is of the form R 2C=S. An intra­molecular O—H⋯N hydrogen bond occurs in each mol­ecule. The crystal structure features weak N—H⋯S inter­actions and π–π stacking of the benzene rings [centroid–centroid distance = 3.667 (3) Å]

Roles of Pro- and Anti-Inflammatory Cytokines in the Pathogenesis of SLE

SLE is an autoimmune inflammatory disease in which various pro- and anti-inflammatory cytokines, including TGF-β, IL-10, BAFF, IL-6, IFN-α, IFN-γ, IL-17, and IL-23, play crucial pathogenic roles. Virtually, all these cytokines can be generated by both innate and adaptive immune cells and exert different effects depending on specific local microenvironment. They can also interact with each other, forming a complex network to maintain delicate immune homeostasis. In this paper, we elaborate on the abnormal secretion and functions of these cytokines in SLE, analyze their potential pathogenic roles, and probe into the possibility of them being utilized as targets for therapy

Cold hardiness of Phauda flammans (Lepidoptera: Zygaenidae) larvae

This study aimed to determine the cold hardiness of Phauda flammans (Lepidoptera: Zygaenidae) larvae. Supercooling points of the 1st–6th instar larvae of P. flammans ranged from –7.7 to –13.0 °C. The lethal temperatures were –8 °C for 1st, –5 °C for 2nd, and –7 °C for 3rd–6th instars. Lethal times at the instar-specific lethal temperatures were 12 h for 1st, 14 h for 2nd, 15 h for 3rd, 17 h for 4th, and 18 h for 5th–6th instars. The times required for all larvae to die in an incubator at 5 °C were 30 d for 1st, 3rd, 4th, and 5th instars, and 25 d for 2nd and 6th instars. The findings suggest that P. flammans is a chill-intolerant species, and larvae will die if the air temperature decreases to –5 to –8 °C for 12–18 h or to 5 °C for 25–30 d. Such conditions are, however, unlikely to occur in southern China

3,3′-Dibenzyl-2,2′-dimethyl-1,1′-methyl­enediimidazolium dipicrate

In the title salt, C23H26N4 2+·2C6H2N3O7 −, the dihedral angle between the imidazolium rings in the dication is 69.9 (1)°. The aromatic ring of the benzyl group is almost perpendicular to the N-heterocyclic ring that is directly connected to it [dihedral angles = 83.2 (2) and 77.3 (3)°]

The genetic diversity and evolutionary history of hepatitis C virus in Vietnam

AbstractVietnam has a unique history in association with foreign countries, which may have resulted in multiple introductions of the alien HCV strains to mix with those indigenous ones. In this study, we characterized the HCV sequences in Core-E1 and NS5B regions from 236 Vietnamese individuals. We identified multiple HCV lineages; 6a, 6e, 6h, 6k, 6l, 6o, 6p, and two novel variants may represent the indigenous strains; 1a was probably introduced from the US; 1b and 2a possibly originated in East Asia; while 2i, 2j, and 2m were likely brought by French explorers. We inferred the evolutionary history for four major subtypes: 1a, 1b, 6a, and 6e. The obtained Bayesian Skyline Plots (BSPs) consistently showed the rapid HCV population growth from 1955 to 1963 until 1984 or after, corresponding to the era of the Vietnam War. We also estimated HCV growth rates and reconstructed phylogeographic trees for comparing subtypes 1a, 1b, and HCV-2

(E)-3-(9-Anthr­yl)-1-(4-fluoro­phen­yl)-2-(4-nitro-1H-imidazol-1-yl)prop-2-en-1-one

In the title compound, C26H16FN3O3, the dihedral angle between the anthryl and fluoro­phenyl groups is 37.8 (1)°. With respect to the imidazolyl group, the twist angles between the imidazolyl group and the anthryl unit and between the imidazoly group and the fluoro­phenyl group are 64.4 (1) and 74.5 (1)°, respectively

Advanced glycation end products accelerate ischemia/reperfusion injury through receptor of advanced end product/nitrative thioredoxin inactivation in cardiac microvascular endothelial cells.

The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population