Lower micromolar activity of the antifungal imidazoles on the bacterial-type bifunctional aldehyde/alcohol dehydrogenase (AdhE) in Cryptosporidium parvum and in vitro efficacy against the zoonotic parasite.

Cryptosporidium parvum is a waterborne and foodborne zoonotic protozoan parasite, a causative agent of moderate to severe diarrheal diseases in humans and animals. However, fully effective treatments are unavailable for medical and veterinary uses. There is a need to explore new drug targets for potential development of new therapeutics. Because C. parvum relies on anaerobic metabolism to produce ATP, fermentative enzymes in this parasite are attractive targets for exploration. In this study, we investigated the ethanol-fermentation in the parasite and characterized the basic biochemical features of a bacterial-type bifunctional aldehyde/alcohol dehydrogenase, namely CpAdhE. We also screened 3892 chemical entries from three libraries and identified 14 compounds showing >50% inhibition on the enzyme activity of CpAdhE. Intriguingly, antifungal imidazoles and unsaturated fatty acids are the two major chemical groups among the top hits. We further characterized the inhibitory kinetics of selected imidazoles and unsaturated fatty acids on CpAdhE. These compounds displayed lower micromolar activities on CpAdhE (i.e., IC50 values ranging from 0.88 to 11.02 µM for imidazoles and 8.93 to 35.33 µM for unsaturated fatty acids). Finally, we evaluated the in vitro anti-cryptosporidial efficacies and cytotoxicity of three imidazoles (i.e., tioconazole, miconazole and isoconazole). The three antifungal imidazoles exhibited lower micromolar efficacies against the growth of C. parvum in vitro (EC50 values ranging from 4.85 to 10.41 µM and selectivity indices ranging from 5.19 to 10.95). The results provide a proof-of-concept data to support that imidazoles are worth being further investigated for potential development of anti-cryptosporidial therapeutics.

Multi-object distance determination by analysis of CoC variation for dynamic structured light.

A multi-object distance determination method can be achieved by 932 nm structured light with one camera as the data receiver. The structured light generated by a liquid crystal on silicon spatial light modulator (LCoS-SLM) facilitates dynamic image projection on targets. A series of moving light strip images were captured and collected for data analysis. This method lifted the limitation of single-object distance determination and the limitation of the angle requirement between the camera and the light source in the triangulation method. The average error of this method was approximately 3% in the range of 700 mm to 1900 mm away from LCoS-SLM without further optimization. It provides a potential compact design for indoor multi-object distance determination in the future.

[Contamination levels of perfluorinated and polyfluoroalkyl compounds in breast milk and assessment of their exposure risk to infants].

The purposes of this study are to explore the contamination levels of perfluorinated and polyfluoroalkyl substances (PFASs) in breast milk and assess their exposure risk to infants. Based on data from a birth cohort study conducted in Yingcheng, Hubei Province, from 2018 to 2021, the contents of 23 types of PFASs in the breast milk of 324 pregnant women were determined using isotope dilution-high performance liquid chromatography-tandem mass spectrometry. Multiple linear regression was then performed to analyze the effects of various demographic characteristics and eating habits on the concentration of PFASs in breast milk. The daily PFASs intake of infants through breast milk was estimated, and the exposure risk of infants was also assessed. The results revealed that 23 types of PFASs in breast milk had good linear relationships in the range of 0.2-100 ng/mL, with correlation coefficients greater than 0.992. The limits of detection were 5-42 pg/mL, the limits of quantification were 15-126 pg/mL, the recoveries were 65.6%-108.1%, and the relative standard deviations were 1.6%-12.8%. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoate acid (PFOA), and perfluorohexanesulfonic acid (PFHxS), with median concentrations of 200.7, 63.5, and 25.2 pg/mL, respectively, were the main PFASs found in breast milk. The detection rates of these three contaminants were higher than 80%, whereas the detection rates of other compounds were lower than 45%. The results of multiple linear regression showed that older pregnant women and a higher frequency of pickled food intake may be related to increased PFAS levels in breast milk whereas a higher frequency of legume intake may be related to decreased PFAS levels in breast milk. The median estimated daily intakes (EDIs) of PFOS, PFOA, and PFHxS for infants were 25.1, 7.9, and 3.2 ng/(kg·d), respectively. In summary, this study found notable PFAS levels in breast milk in Yingcheng, Hubei Province. Among these PFASs, PFOS, PFOA, and PFHxS were the main contaminants. Maternal age as well as pickled food and legume intake may affect the PFAS level in breast milk. The health risk of PFAS intake through breast milk to some infants is worthy of attention and further study.

The effects of novel chitosan-targeted gemcitabine nanomedicine mediating cisplatin on epithelial mesenchymal transition, invasion and metastasis of pancreatic cancer cells.

OBJECTIVE: The study aimed to evaluate the effects involved with the novel chitosan gemcitabine (Gem) nanoparticles mediating cisplatin (DDP) on epithelial mesenchymal transition (EMT), invasion and metastasis of pancreatic cancer (PC) cells. METHODS: A total of 62 healthy purebred BALB/C of specific-pathogen free (SPF) female nude mice were recruited and a SW1990 cell line was subsequently cultured. A heterotopic xenograft tumor model was constructed. After determining the optimal drug concentration, the nude mice were assigned into the control, glycol chitosan (GC)-Gem microsphere, antibody Complex (Abc)-GC-Gem and Abc-GC-Gem microsphere+DDP groups (n=8 in each group). The tumor morphology of the nude mice was observed and HE staining was used to observe the pathological changes of the respective tissues. TUNEL staining was performed to detect cell apoptosis, while immunohistochemistry was employed for analysis of the positive expression rate of EGFR and the number of microvessel density (MVD). Both RT-qPCR and Western blotting were utilized for mRNA and protein expressions of VEGF, EGFR, Bcl-2, Bax, Survivin, Bak, E-cadherin and Vimentin analysis. RESULTS: The optimal drug concentration of Gem was determined to be 120mg/m2. In comparison to the control group, tumor size, weight, positive expression rate of EGFR and tumor MVD, as well as mRNA and protein expressions of Bax and E-cadherin decreased, while the inhibition rate (IR) and apoptosis index (AI), expression of VEGF, EGFR, Bcl-2, Survivin, Bak and Vimentin increased in the GC-Gem microsphere, Abc-GC-Gem microsphere and Abc-GC-Gem microsphere+DDP groups. Compared with the GC-Gem microsphere group, Abc-GC-Gem and Abc-GC-Gem microsphere+DDP groups had decreases concerning tumor size and weight, positive rate of protein expression of EGFR and tumor MVD, as well as the expression of Bax and E-cadherin, and enhances on IR and AI, expression of VEGF, EGFR, Bcl-2, Survivin, Bak, and Vimentin, which were the most obvious in the Abc-GC-Gem+DDP group (P<0.05). CONCLUSION: Novel Gem nanoparticles aid in mediating DDP to inhibit PC cell invasion and migriation, promote PC cell apoptosis and enhance the efficacy of chemotherapy. Our findings demonstrated that Gem administered in combination with DDP was more effective than Gem alone.

Effects of microRNA-183 on epithelial-mesenchymal transition, proliferation, migration, invasion and apoptosis in human pancreatic cancer SW1900 cells by targeting MTA1.

OBJECTIVE: This study aims to explore effects of miR-183 on epithelial-mesenchymal transition (EMT) and invasion by targeting MTA1 in human pancreatic cancer (PC) cells. METHODS: Totally, 108 PC patients admitted in Wenzhou Central Hospital and Wenzhou People's Hospital, The Dingli Clinical Institute of Wenzhou Medical University from March 2010 to March 2014 were enrolled. qRT-PCR and immunohistochemistry were applied to examine expression of MTA1 mRNA and protein. Samples were divided into 6 groups: blank, NC, miR-183 mimics, miR-183 inhibitors, MTA1-siRNA and miR-183 inhibitors +MTA1-siRNA groups. CCK8 method was employed for determining cell proliferation rate, flow cytometry for cell apoptosis rate, scratch test for cell migration and Transwell assay for cell invasion. qRT-PCR and Western blotting were used to determine expression of MTA1, E-cadherin and Vimentin mRNA and protein. RESULTS: Positive expression rate of MTA1 was upregulated in PC tissues, and expression of miR-183 and MTA1 was associated with differentiation, migration, tumor size, TNM. The miR-183 mimics and MTA1-siRNA groups showed a decrease in proliferation, migration and invasion, whereas increased apoptosis, in comparison with blank and NC groups, as expression of MTA1 and Vimentin mRNA and protein were reduced, expression of E-cadherin mRNA and protein was elevated. Compared to blank and NC groups, the miR-183 inhibitors group exhibited enhanced proliferation, migration and invasion and inhibited apoptosis; increased expressions of MTA1 and Vimentin mRNA and protein and decreased expressions of E-cadherin mRNA and protein. CONCLUSION: Our study supported that miR-183 could repress EMT and invasion of human PC cells through inhibition of MTA1 expression.

A rare case of gangrene of cystic duct due to the insertion of endoscopic nasobiliary drainage (ENBD) tube into the cystic duct by mistake

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A rare case of gangrene of cystic duct due to the insertion of endoscopic nasobiliary drainage (ENBD) tube into the cystic duct by mistake.

This is the first case report of Gangrenous cholecystitis due to the insertion of endoscopic nasobiliary drainage (ENBD) tube into the cystic duct by mistake,The reason why it happened may be related to Inflammation and hypoimmunity.

Insight into the mechanical, thermodynamics and superconductor properties of NbRuB via first-principles calculation.

Using the first-principles calculations, the electronic structure, chemical bonding, mechanical, thermodynamics and superconductor properties of NbRuB are investigated. The optimized lattice parameters were in good agreement with the experimental data. The analysis of the density of states and chemical bonding implies that the metallic behavior of NbRuB originates from the Ru and Nb, and the bonding behaviors are a mixture of covalent-ionic bonds. The bulk modulus, shear modulus, Young's modulus, Poisson's ratio and hardness of NbRuB were calculated. The results reveal that the NbRuB is ductility and the Vickers hardness is 15.06 GPa. Moreover, the 3D dependences of reciprocals of Young's modulus is also calculated and discussed, showing strong anisotropic character for NbRuB. Finally, the Debye temperature and superconducting transition temperature are obtained.

(Z)-1,4-Diphenyl-but-1-en-3-ynyl acetate.

The title compound, C(18)H(14)O(2), is almost planar with a dihedral angle of 1.24 (2)° between the phenyl-ethynyl and styryl groups. The acet-oxy group is tilted by 82.46 (2) and 82.26 (3)° with respect to the benzene ring planes.

[An experiment to study the treatment of sarcomas by electroporation].

In this paper is reported a new approach for the treatment of sarcoma--electroporation therapy. Electroporation can accelerate pharmacal molecules into cytoplasm by transient electromagnetic pulses. We have utilized the phenomenon of electroporation treating the S-180 sarcomas in the hind legs of the Kunming mice by intratumoral injection of anti-tumor agent at low dose. From the experiment, we learned that this approach can bring about remarkable effect. The technical procedure is easy to do and easy to control. Especially, it is useful in curing the flat tumor and has little untoward side effect. It deserves to be recommended as a new approach to treating the tumor in clinics.

[Enhancing the cytotoxicity of antitumor drugs through electromagnetic pulses].

We chose Hela cells as research object and studied the cytotoxicity generated by cyclophosphamide, an antitumor drug, after cell electroporation by the use of electromagnetic pulses. Comparison between the electroporation group and the contrast group revealed the greatly enhanced cytotoxicity of the electroporation group, indicating that under some conditions electromagnetic pulses can enhance the cytotoxicity of antitumor drugs. The results of this study provide reliable evidences and a feasible approach for clinical treatment of tumor.

[Study of high-intensity electric pulse inhibited sarcoma for improving antitumor drug effect].

This article reports the experiment studies on treating the S-180 sarcomas of KM mice with high-intensity electric pulse and antitumor drug (cyclophosphamide). The results showed that the experimental group of electric field combined with drug has the best effect on tumor, compared with the control group. In addition, electric field can inhibit the formation of vas Capillaries and decrease the supply of nutrition for tumor cell. In conclusion, electric field has inhibited the growth of tumor.