Eradication of growth of HER2-positive ovarian cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate in mouse xenograft model.

OBJECTIVE: Ovarian cancer is 1 kind of a highly malignant gynecologic tumor, and current treatments have not achieved satisfactory effects. Human epidermal growth factor receptor 2 (HER2)-targeted therapies including trastuzumab and trastuzumab-DM1 (T-DM1) (antibody-cytotoxic drug conjugates) have been applied to treat HER2-overexpressing breast cancers in clinic. In the present study, we explored whether T-DM1 could effectively treat HER2-positive human ovarian carcinoma in vitro and in vivo. METHODS: HER2 expressions of 6 ovarian cancer cell lines and 2 breast carcinoma cell lines were validated, and the binding capacity of T-DM1 to HER2-positive ovarian cancer SKOV3 cells were analyzed by flow cytometry. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effect of T-DM1. RESULTS: High HER2 expressions in SKOV3 cell lines were detected. The binding capacity of T-DM1 to HER2-positive SKOV3 cells was in a similar manner comparing with trastuzumab. In vitro, T-DM1 showed strong growth inhibitory on SKOV3 cells, with IC50 values of 0.15 nmol/L. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effects of T-DM1 in vivo. In subcutaneous xenografts model, T-DM1 (30 mg/kg and 10 mg/kg) indicated significant anticancer effects. It is noteworthy that tumors were completely eradicated in the T-DM1 (30 mg/kg) group, and no regrowth was observed in a long time after the termination of the treatment. In the peritoneal xenograft model, tumor nodules in 3 of 7 mice were hardly observed in the abdominal cavity of mice after intraperitoneal injection of T-DM1 (30 mg/kg). At the same time, tumor nodules from the other 4 mice weighed on the average of only 0.07 g versus 1.77 g in control group. CONCLUSIONS: Our data showed that T-DM1 possessed promising antitumor effects on HER2-overexpressing ovarian cancer in mouse model, which provided valuable references for the future clinical trials.

A sensitive fluorometric-colorimetric dual-mode intelligent sensing platform for the detection of formaldehyde.

Excess formaldehyde (FA) is a strong carcinogen, so the development of a rapid visualized and portable formaldehyde detection platform is of great research importance. A multi-color fluorescence sensing system constituted of model compound (NAHN) and red-emitting InP/ZnS QDs was constructed herein, which can simultaneously realize fluorometric-colorimetric dual-mode sensing when exposed to FA environment. Its preparation process was simplified, the detection process was green, and the limits of detection (LOD) were 0.623 µM and 0.791 µM, respectively. The high recoveries of FA in actual water samples indicated that the sensor had broad application prospects. The prepared fluorescent film can be utilized for rapid visual simulation analysis of FA on the surface of various fruits and vegetables. In addition, a serial logic gate was designed to quickly semi-quantitatively assess FA concentration, which promoted the realization of on-site intelligent evaluation of FA.

Molecular and morphological evidence support a new species of RosaceaePrunus subg. Cerasus from Wuyishan National Park, southeast China.

Prunustongmuensis, a new species of cherry blossom, is described and illustrated from Wuyishan National Park, southeast China. This species is characterized by its tubular to nearly bottle-shaped receptacles and dark purple drupes. It can be distinguished from other wild cherry trees by its flowers and leaves, reddish brown young leaves, presence of 1-2 glands at the base of leaves, petioles densely covered with yellowish brown villi, longer pedicels (0.6-2.5 cm), villous pistil, and dark purple drupes. In the present study, we conducted a comprehensive morphological study based on specimens of the new species and its morphologically close species, field observations, and examination of pollen morphology. In addition, our phylogenetic analysis based on the complete plastid genome sequences further confirms the status of the new species and indicates that it is closely related to Prunusclarofolia, however, it notably differs in leaf shape, size, petiole villus color, gland location, timing of flower and leaf openings, and reflexed or spread sepals, as well as drupe color.

Population Variation and Phylogeography of Cherry Blossom (Prunus conradinae) in China.

Prunus conradinae (subgenus Cerasus, Rosaceae) is a significant germplasm resource of wild cherry blossom in China. To ensure the comprehensiveness of this study, we used a large sample size (12 populations comprising 244 individuals) which involved the fresh leaves of P. conradinae in Eastern, Central, and Southwestern China. We combined morphological and molecular evidence (three chloroplast DNA (cpDNA) sequences and one nuclear DNA (nr DNA) sequence) to examine the population of P. conradinae variation and differentiation. Our results revealed that Central, East, and Southwest China are important regions for the conservation of P. conradinae to ensure adequate germplasm resources in the future. We also found support for a new variant, P. conradinae var. rubrum. We observed high genetic diversity within P. conradinae (haplotype diversity [Hd] = 0.830; ribotype diversity [Rd] = 0.798), with novel genetic variation and a distinct genealogical structure among populations. There was genetic variation among populations and phylogeographic structure among populations and three geographical groups (Central, East, and Southwest China). The genetic differentiation coefficient was the lowest in the Southwest region and the gene exchange was obvious, while the differentiation was obvious in Central China. In the three geographic groups, we identified two distinct lineages: an East China lineage (Central China and East China) and a Southwest China lineage ((Central China and Southwest China) and East China). These two lineages originated approximately 4.38 million years ago (Mya) in the early Pliocene due to geographic isolation. P. conradinae expanded from Central China to East China at 3.32 Mya (95% HPD: 1.12-5.17 Mya) in the Pliocene. The population of P. conradinae spread from East China to Southwest China, and the differentiation time was 2.17 Mya (95% (HPD: 0.47-4.54 Mya), suggesting that the population of P. conradinae differentiated first in Central and East China. The population of P. conradinae experienced differentiation from Central China to Southwest China around 1.10 Mya (95% HPD: 0.11-2.85 Mya) during the early Pleistocene of the Quaternary period. The southeastern region of East China, near Mount Wuyi, likely serves as a refuge for P. conradinae. This study establishes a theoretical foundation for the classification, identification, conservation, and exploitation of germplasm resources of P. conradinae.

Dual-Channel Probe of Carbon Dots Cooperating with Lanthanide Complex Employed for Simultaneously Distinguishing and Sequentially Detecting Tetracycline and Oxytetracycline.

Tetracycline (TC) and oxytetracycline (OTC) are the most widely used broad-spectrum antimicrobial agents in tetracycline drugs, and their structures and properties are very similar, so it is a great challenge to distinguish and detect these two antibiotics with a single probe at the same time. Herein, a dual-channel fluorescence probe (SiCDs@mMIPs-cit-Eu) was developed by integrating two independent reaction sites with SiCDs-doped mesoporous silica molecular imprinting group and europium complex group into a nanomaterial. The synergistic influence of inner filter effect and "antenna effect" can be guaranteed to solve the distinction between TC and OTC. Moreover, this novel strategy can also sequentially detect TC and OTC in buffer solution and real samples with high sensitivity and selectivity. This method revealed good responses to TC and OTC ranging from 0 to 5.5 µM with a detection limit of 5 and 16 nM, respectively. Combined with the smartphone color-scanning application, the portable and cheap paper-based sensor was designed to realize the multi-color visual on-site detection of TC and OTC. In addition, the logic gate device was constructed according to the fluorescence color change of the probe for TC and OTC, which provided the application possibility for the intelligent detection of the probe.

A smartphone-integrated multicolor fluorescence probe of bacterial spore biomarker: The combination of natural clay material and metal-organic frameworks.

The metal-organic frameworks (MOFs) functionalized palygorskite (Pal) hybrid as a novel multicolor fluorescence probe for the detection of bacterial spore biomarker-dipicolinic acid (DPA), had been prepared via in-situ growth. The MOFs can effectively encapsulate dye molecules on the surface of Pal, and the rich carboxyl groups on its surface can coordinate with europium ions (Eu3+), forming a highly sensitive recognition group. The results indicated that the limit of detection (LOD) of this multicolor fluorescence probe was as low as 9.3 nM and was obviously lower than the amount of anthrax spores infecting the human body (60 µM). Moreover, a wide linear range from 0 to 35 µM was obtained. The high specific surface area of Pal, as well as the permanent porosity and suitable binding sites of Eu3+-doped MOFs may play a major role in the sensitivity and linear detection range. The multicolor fluorescence strategy made full use of the diversity of fluorescence signals collected by dye molecules and lanthanide ions, which can realize the real-time and on-site detection through the smartphone with a color-scanning application (APP). The practicability of this probe was further verified by detecting DPA released by non-infectious Bacillus subtilis.

Ultrasensitive and visual detection of tetracycline based on dual-recognition units constructed multicolor fluorescent nano-probe.

Ultrasensitive and visual detection of tetracycline antibiotic (TC) residues is of great significance to public health and environmental safety. A novel dual-response ratiometric fluorescent nano-probe (SiQDs-Cit-Eu) has been elaborately tailored for the determination and on-site visual assay of tetracycline, by grafting citric acid and europium (Eu3+) ions onto the surface of silicon quantum dots (SiQDs). The blue-emissive SiQDs (λem = 455 nm) fabricated by a one-step facile method act as both scaffold for coordination with Eu3+ ions and recognition unit for TC owing to the inner filter effect (IFE). The coordinate unsaturated red-fluorescent Eu3+ ions (λem = 617 nm) bond to the surface of SiQDs, serving as the specific recognition element for TC due to the antenna effect. In the presence of TC, the as-synthesized nano-probe exhibits double (λem = 455 and 617 nm) and reverse response signals which are accompanied by a marked color change from blue to purple, and then red, thus achieving ultra-high sensitivity with a detection limit of 7.1 nM and instant visual detection of TC in real samples (milk, honey, lake and river water). Furthermore, smartphone-assisted point-of-care testing platform is also constructed based on nano-probe-immobilized test paper by using the color scanning APP.

A stick-like intelligent multicolor nano-sensor for the detection of tetracycline: The integration of nano-clay and carbon dots.

In recent years, the overuse of antibiotics has caused more and more serious environmental pollution, the uncontrolled abuse of antibiotics makes bacteria produce resistance to antibiotics faster than the replacement rate of antibiotics themselves, leading to the emergence of super drug-resistant bacteria. Therefore, it is of great practical significance to establish a simple, rapid and sensitive method for the detection of antibiotics. By integrating natural nano-clay (Atta) and carbon dots (CDs), the real-time and rapid visual detection of tetracycline (TC) in the sample can be realized by chromaticity pick-up APP on smartphone. The nano-sensor can detect tetracycline in the concentration between 25 nM and 20 µM with the detection limit of 8.7 nM. The low detection limit coupled with good accuracy, sensitivity and specificity meets the requirements for the detection of tetracycline in food. More importantly, the test paper and fluorescent stick-like nano-sensor are designed to detect tetracycline by polychromatic fluorescence changes. In addition, a logic gate for semi-quantitative identification of the concentration of tetracycline is designed, which makes it possible for the application of the nano-sensor in the field of smart devices.

A Ratiometric Fluorescent Nano-Probe for Rapid and Specific Detection of Tetracycline Residues Based on a Dye-Doped Functionalized Nanoscaled Metal-Organic Framework.

Tetracycline (TC) residues are harmful to the environment and human body, so it is necessary to develop a highly sensitive probe for rapid detection of tetracycline residues. In the present paper, a novel dye-doped porous metal-organic framework (UiO-66)-based multi-color fluorescent nano-probe was designed for sensitive ratiometric detection of tetracycline (TC). In this probe, dye-molecules doped UiO-66 was used as a fluorescent internal standard, and the externally grafted lanthanide Eu3+ complex was used as response signals. The fluorescence of the Eu3+ complex was selectively enhanced with increasing concentrations of TC, which was accompanied by a visual blue-to-red color switch. The nano-probe had a linear response between 0.1 and 6 µM with a lowest detection limit of 17.9 nM, which was much lower than the maximum residue limits set by the United States Food and Drug Administration (676 nM) and the European Union (225 nM). The applicability of this method in the analysis of actual samples was evaluated by the determination of TC in honey and milk samples, indicating satisfactory recovery and good reproducibility. In addition, a cost-effective paper-based probe for rapid and visual detection of TC was developed by fixing the nano-probe on filter papers. With the help of a smartphone camera to capture the fluorescence color, and chromaticity analysis software, the calculation and analysis of red (R) and blue (B) values can be realized, which has the potential for real-time visual detection of TC.

miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells.

Increasing evidence in the past few years has shown that miRNAs could serve functionally as "oncogenes" or "tumor suppressor genes" and regulate multiple cellular processes relevant to carcinogenesis and cancer progression. Both RhoA and Cdc42, two members of the Rho GTPase family, are found to be upregulated in several types of human tumors including colorectal cancer, and have been implicated in cancer initiation and progression. In the present studies, we found that miR-185 expression greatly inhibited the proliferation potential of Hela cells. An examination of the predicted targets of miR-185 revealed RhoA and Cdc42 among the putative targets that are crucial for cell proliferation. A genomic sequence analysis indicated that nt 1844-1852 of the RhoA 3'UTR and nt 1382-1396 of the cdc42 3'UTR encode for miR-185 target matching sequences and they are highly conserved across different species. Using a luciferase-reporter assay, we show that miR-185 expression significantly suppressed the RhoA and Cdc42 3'UTR activities, and the inhibitory effect was lost when the putative target sites for miR-185 were mutated. Consistent with these results, ectopic expression of miR-185 reduced protein levels of RhoA and Cdc42 in cells, indicating miR-185 functionally regulates RhoA and Cdc42 abundance. Similar to the effects of knocking down RhoA and/or Cdc42 expression, miR-185 effectively inhibited proliferation, induced G1 cell cycle arrest and apoptosis, and blocked invasion of colorectal cancer cells. Thus, miR-185 is a negative regulator of RhoA and Cdc42 and their cellular activities, and could inhibit proliferation and invasion of colorectal cancer cells.