Highly Water-Soluble Cucurbit[8]uril Derivative as a Broad-Spectrum Neuromuscular Block Reversal Agent.

Broad-spectrum agents for the reversal of residual curarization induced by neuromuscular blocking agents are of great significance. Here, we report a highly water-soluble cucurbit[8]uril (CB[8]) derivative as a broad-spectrum neuromuscular block reversal agent induced by both benzylisquinolinium and aminosteroid neuromuscular block agents by the supramolecular sequestration strategy. The UV/Vis competition titration assays suggest the high binding affinity of the CB[8] derivative toward both benzylisquinolinium-type cisatracurium besylate and aminosteroid-type rocuronium, vecuronium, and pancuronium, at the level of 107 M-1. In vivo studies demonstrate that the administration of the CB[8] derivative could significantly accelerate the recovery time compared to the placebo or neostigmine groups. The reversal activity of the CB[8] derivative is comparable to or higher than that of clinically approved sugammadex. Acute toxicity evaluations reveal that the CB[8]-derivative displays outstanding biocompatibility, with the maximum tolerance dose as high as 960 mg kg-1.

Flexible organic frameworks sequester neuromuscular blocking agents in vitro and reverse neuromuscular block in vivo.

Supramolecular sequestration and reversal of neuromuscular block (NMB) have great clinical applications. Water-soluble flexible organic frameworks (FOFs) cross-linked by disulfide bonds are designed and prepared. Different linker lengths are introduced to FOFs to give them varied pore sizes. FOFs are anionic nanoscale polymers and capable of encapsulating cationic neuromuscular blocking agents (NMBAs), including rocuronium (Roc), vecuronium (Vec), pancuronium (Panc) and cisatracurium (Cis). A host-guest study confirms that FOFs bind NMBAs in water. The multivalency interaction between FOFs and NMBAs is able to sequester NMBAs, and prevent them from escaping. These FOFs are non-toxic and biocompatible. Animal studies show that FOFs are effective for the reversal of NMB induced by Roc, Vec and Cis, which shorten the time to a train-of-four ratio of 0.9 by 2.6, 3.8 and 5.7-fold compared to a placebo, respectively.

Olive-Shaped Organic Cages: Synthesis and Remarkable Promotion of Hydrazone Condensation through Encapsulation in Water.

Two organic cages have been prepared in situ in water through the 2 + 3 hydrazone coupling of two pyridinium-derived trialdehydes and oxalohydrazide. The highly water-soluble cages encapsulate and solubilize linear neutral molecules. Such encapsulation has been applied for the promotion of both two- or three-component hydrazone condensation in water. For two-component reactions, the yields of the resulting monohydrazones are increased from 5-10 to 90-96%. For three-component reactions of hydrazinecarbohydrazide with 11 aromatic aldehydes, in the presence of the organic cages, the bihydrazone products can be produced in 88-96% yields. In contrast, without the promotion of the organic cages, 9 of the reactions do not afford the corresponding dihydrazone product.

Flexible Organic Framework-Based Anthracycline Prodrugs for Enhanced Tumor Growth Inhibition.

A water-soluble flexible organic framework FOF-hz of low cytotoxicity has been synthesized from a pyridinium-derived tetracationic tetraaldehyde and a citric acid-derived tritopic acylhydrazine (1:2) through the formation of a hydrazone bond. Dynamic light-scattering experiments reveal that FOF-hz has a hydrodynamic diameter of 79 nm at 0.1 mM concentration of the tetrahedral precursor. Dialysis experiments show that the free acylhydrazine units of FOF-hz can react with the C-13 ketone units of anthracycle drugs, including doxorubicin (DOX), daunorubicin, epirubicin, and pirarubicin, at pH = 3.0 to conjugate the drugs in 78-85% yields. The resulting FOF-prodrugs exhibit remarkable acid-responsive deconjugation of the conjugated active agents. Laser confocal scanning microscopy and flow cytometric analysis support that FOF-hz displays enhanced permeability and retention effect, which helps to overcome the multidrug resistance of MCF-7/ADR tumor cells and leads to enhanced cytotoxicity for MCF-7/ADR cells. In vivo studies reveal a considerable improvement of the efficacy of the prodrug FOF-DOX for the inhibition of the growth of the MCF-7/ADR tumor.

Extensive disseminated cysticercosis: a case report in Yunnan province, China.

BACKGROUND: Cysticercosis is spreading all over the world and it is a major health problem in most countries of Latin America, Africa, and Asia. Extensive disseminated cysticercosis is relatively rare and fewer than 120 case have been reported in the worldwide. We reported a rare case of extensive disseminated cysticercosis in Yunan province, China. CASE PRESENTATION: A rare case of extensive disseminated cysticercosis, in a 61-year-old male Chinese was detected from Yunnan province in 2018. Clinical and etiological examination was performed, as well as the epidemiological investigation. CONCLUSION: The life cycle of T. solium in the area where the case came from is complete. We expect this case could raise the attentions to the control of Taenia solium infection and subsequent cysticercosis there.

Overexpression of CHD1L is associated with poor survival and aggressive tumor biology in esophageal carcinoma.

Esophageal carcinoma (EC) is a malignancy with high metastatic potential. Chromosomal helicase/ATPase DNA binding protein 1-like (CHD1L) gene is a newly identified oncogene located at Chr1q21, and it is amplified in many solid tumors. However, the status of CHD1L protein expression in EC and its clinical significance is uncertain. This study was designed to investigate the significance of CHD1L expression in human EC and its biological function in EC cells. The expression of CHD1L was examined by immunohistochemistry in 191 surgically resected ECs. The associations between CHD1L expression and clinical pathological parameters and the prognostic value of CHD1L were analyzed. Western blot analysis showed that CHD1L was overexpressed in EC cell lines. In addition, positive CHD1L expression was strongly related to advanced clinical stage (P<0.01), and lymph node metastasis (P<0.01) of EC. The Kaplan-Meier curve indicated that high expression of CHD1L may result in poor prognosis of EC patients (P<0.01), and multivariate analysis showed that CHD1L overexpression was an independent predictor of overall survival. Furthermore, suppression of CHD1L in EC cells increased apoptosis and decreased cell proliferation invasion ability. Our results suggest that CHD1L is a target oncogene with the potential to serve as a novel prognostic biomarker in EC pathogenesis.

[Comparison between albendazole and triclabendazole against Fasciola gigantica in human].

OBJECTIVE: To compare the anthelmintic effect of albendazole with that of triclabendazole against Fasciola gigantica. METHODS: Two patients infected with Fasciola gigantica were investigated, and one was administered with albendazole orally (200 mg, twice per day for 5 days) and another was administered with triclabendazole [10 mg/(kg x d) for 2 days]. Their total feces were collected daily during the period of whole therapy, and the eggs of the parasite were collected by using the nylon bag method, and incubated at 28 degrees C. RESULTS: The parasite eggs were detected from the first patient's dejecta on the 1st, 2nd and 5th day after the end of the treatment, and no miracidiums hatched out as well as no eggs developed during the period of 25 days of the incubation. Meanwhile, her body temperature fluctuated between 37.4 degrees C and 38.3 degrees C, and she still complained bellyache. For the other invalid, the eggs were not detected on the 2nd and 5th day after the end of the treatment. However, the eggs before and during the treatment developed the miracidiums of Fasciola gigantica on the 13th day after the incubation, but the eggs collected from the 1st day after the termination of the therapy did not develop and no miracidiums hatched out. At the same time, the signs and symptoms of the patient vanished after the 4th day of the end of the therapy. CONCLUSIONS: Albendazole has no obvious insecticidal activity on adult Fasciola gigantica in the short term, but may affect the development of eggs. Triclabendazole has the anthelmintic effect on the adults as well as eggs of Fasciola gigantica. In addition, triclabendazole has the characteristics of well curative effect, short course of treatment, and no obvious side effects.

[Survey of the number of eggs in Taenia asiatica gravid proglottids in Dali Prefecture of Yunnan Province].

OBJECTIVE: To observe the number of eggs in the gravid proglottids of Taenia asiatica. METHODS: Twenty gravid proglottids at each end of two adults of T. asiatica were digested by 1% pepsin. Then, the collected eggs were observed and counted by a microscope. RESULTS: The number of eggs in each gravid proglottid were not the same, with the maximum of 132 500, minimum of 44 180, and the average number of 90 051, and there was a significant difference among the different gravid proglottids (t = -3.487, P = 0.003). CONCLUSION: The number of eggs in different gravid proglottids of T. asiatica is evidently different.

[Investigation on Taenia sp. infection in Midu County of Yunnan Province].

The current status and species of Taenia sp. were investigated in Midu County by sedimentation method to examine eggs of Taenia sp. in stool, questionnairing as well as deworming by areca-pumpkin seeds in October-December, 2010. The infection rate of Taenia sp. was 15.7% (65/414). Among the positives, it was fairly high in the age groups of 40- and 50-, being 24% (21/85) and 26% (15/57), respectively. 26 cases with positive stool examination and 47 cases with a history of discharging proglottids were treated. Adult worms were collected from all 26 egg positive cases and 23 persons discharging proglottids. The highest number of adult worms expelled was 11 in a woman, 2 worms from another villager, but only one worm each from all other cases. 15 tapeworms with scolex and mature proglottids were examined and morphologically identified as T. asiatia. The high prevalence was related to the residents' dietetic habits (eg. eating raw pork and liver) , behaviour (eg. defecating in field) , and the egg-contaminated environment (eg. by untreated feces).

Onset of cooperation between layered networks.

Functionalities of a variety of complex systems involve cooperations among multiple components; for example, a transportation system provides convenient transfers among airlines, railways, roads, and shipping lines. A layered model with interacting networks can facilitate the description and analysis of such systems. In this paper we propose a model of traffic dynamics and reveal a transition at the onset of cooperation between layered networks. The cooperation strength, treated as an order parameter, changes from zero to positive at the transition point. Numerical results on artificial networks as well as two real networks, Chinese and European railway-airline transportation networks, agree well with our analysis.

[Characterization of expression of alpha1-acid glycoprotein gene in Beijing fatty chicken (Gallus gallus)].

The specific expression of alpha1-AGP gene in eight different tissues of Beijing fatty chicken was investigated by RT-PCR. The full-length cDNA of alpha1-AGP was inserted into pEGFP-C1 multi-cloning sites to construct recombinant eukaryotic expression vector pEGFP-alpha1-AGP. The lipofectin method was used to transfect the pEGFP-alpha1-AGP into Beijing fatty chicken fibroblast cells. The open reading frame of Beijing fatty chicken alpha1-AGP gene was 612 base pairs in length, which was expressed higher in liver and lung than in muscle. This gene did not express in heart and kidney. The expression efficiency ranged from 31.3% to 47.6% in 24, 48, and 72 h after transformation. The green fluorescence mainly concentrated in the nucleus. With the increase of the expression of green fluorescence, granula was observed in the nucleus. RT-PCR and Western blotting analyses showed that pEGFP-alpha1-AGP had been integrated into the genome of Beijing chicken fibroblast cell with normal expression level. In optimized condition, there was no significant effect (P>0.05) on apoptosis ratio, positive cell shape, growth and reduplication state comparing with the control group. This research established the foundation for further function research of alpha1-AGP gene and application in transgenic animal cloning.