Functional polymeric molecules for performing autonomous synthesis of particles with core-shell structures and customizable shapes.

Self-organization by the directed migration of components within a system is an important process in many applications, such as the unidirectional migration of motor proteins for transporting items to specific sites in a cell. This manuscript describes a class of functional polymeric molecules that have a set of instructions written by specific chemical moieties. These instructions allow the functional polymeric molecules to be used for autonomous synthesis of particles: particles with both functional core-shell structure and customizable shapes are fabricated for the first time. The functional polymeric molecules direct the large-scale migration of the liquid molecules to specific sites for forming the required customized structure of the particle, thus overcoming previous challenges of fabricating this class of particles. This first synthesis of this class of particles enables the development of novel applications: the concept of shape specificity for targeting sites. Both the basic structural properties (core-shell structure and customizable shape) are used in the specific applications of targeted drug delivery and imaging. The secure physical fit due to the complementary shapes enables the particles to remain locked in position for the targeting. Polymeric molecules are first shown to be highly capable of being encoded with instructions for autonomous synthesis of structured materials.

Intermittent spontaneous ovulation in patients with premature ovarian failure: Three case reports and review of literature.

BACKGROUND: Premature ovarian failure (POF) is the end-stage of a decline in ovarian function prior to the age of 40 years that involves symptoms associated with low estradiol (E2) levels and a minimal probability of pregnancy. This increases the physical and psychological burden experienced by young women of reproductive age, particularly with regards to over-diagnosis. CASE SUMMARY: Here, we report three cases (29, 22, and 33 years-of-age) diagnosed with POF after experiencing secondary amenorrhea for more than one year, serum levels of follicle-stimulating hormone (FSH) > 40 IU/L on two occasions with an interval of more than 4 wk, and negative progesterone withdrawal tests. All three patients were intermittently administered with drugs to create an artificial cycle. During the subsequent discontinuation period, the patients experienced intermittent follicular growth and spontaneous ovulation. One patient experienced two natural pregnancies (both with embryo arrest). CONCLUSION: Our findings suggest that young patients with POF can experience unpredictable and intermittent spontaneous follicular development, ovulation, and even natural pregnancy. Clinicians should provide appropriate medical guidance and individualized treatments according to fertility requirements, genetic risks and hypoestrogenic symptoms as soon as possible.

Crosstalk between PML and p53 in response to TGF-ß1: A new mechanism of cardiac fibroblast activation.

Cardiac fibrosis is a common pathological cardiac remodeling in a variety of heart diseases, characterized by the activation of cardiac fibroblasts. Our previous study uncovered that promyelocytic leukemia protein (PML)-associated SUMO processes is a new regulator of cardiac hypertrophy and heart failure. The present study aimed to explore the role of PML in cardiac fibroblasts activation. Here we found that PML is significantly upregulated in cardiac fibrotic tissue and activated cardiac fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). Gain- and loss-of-function experiments showed that PML impacted cardiac fibroblasts activation after TGF-ß1 treatment. Further study demonstrated that p53 acts as the transcriptional regulator of PML, and participated in TGF-ß1 induced the increase of PML expression and PML nuclear bodies (PML-NBs) formation. Knockdown or pharmacological inhibition of p53 produced inhibitory effects on the activation of cardiac fibroblasts. We further found that PML also may stabilize p53 through inhibiting its ubiquitin-mediated proteasomal degradation in cardiac fibroblasts. Collectively, this study suggests that PML crosstalk with p53 regulates cardiac fibroblasts activation, which provides a novel therapeutic strategy for cardiac fibrosis.

One-pot mechanochemical synthesis to encapsulate functional guests into a metal-organic framework for proton conduction.

Through one-pot mechanochemical synthesis, a series of guests [imidazole, (aminomethyl)phosphonic acid, urea and sulfamic acid] are rapidly encapsulated into the pores of MOF NENU-3 while the MOF is formed. The synthesis of a MOF loaded with functional guests that used to take several days and require a multistep procedure can now be completed in one step within several minutes. The proton conductivities of the obtained composites increased by 2-3 orders of magnitude compared with NENU-3.

Fluorofenidone inhibits epithelial-mesenchymal transition in human lens epithelial cell line FHL 124: a promising therapeutic strategy against posterior capsular opacification.

PURPOSE: The present study aimed to investigate the inhibitory effect of fluorofenidone against transforming growth factor ß2-induced proliferation and epithelial-mesenchymal transition in human lens epithelial cell line FHL 124 and its potential mechanism. METHODS: We evaluated the effect of fluorofenidone on proliferation and epithelial-mesenchymal transition of human lens epithelial cell line FHL 124 in vitro. After treatment with 0, 0.1, 0.2, 0.4, 0.6, and 1.0 mg/mL fluorofenidone, cell proliferation was measured via MTT assay. Cell viability was evaluated by lactate dehydrogenase activity from damaged cells. FHL 124 cells were treated with different transforming growth factor ß2 concentrations (0-10 ng/mL) for 24 h and the expression of CTGF, α-SMA, COL-I, E-cadherin, and Fn were detected via quantitative polymerase chain reaction and Western blot analysis. After treatment with 0, 0.2, and 0.4 mg/ml fluorofenidone, the expressions of transforming growth factor ß2 and SMADs were detected with real-time polymerase chain reaction and Western blot analysis. Expressions of CTGF, α-SMA, COL-I, and Fn were analyzed by immunocytochemistry assay. RESULTS: The viability of FHL 124 cells was not inhibited when the fluorofenidone concentration was ≤0.4 mg/mL after the 24h treatment. Cytotoxicity was not detected via lactate dehydrogenase assay after the 24h and 36h treatment with 0.2 and 0.4 mg/mL fluorofenidone. Transforming growth factor ß2 increased mRNA and protein expression of CTGF, α-SMA, COL-I, and Fn. However, fluorofenidone significantly suppressed expression of SMADs, CTGF, α-SMA, COL-I, and Fn in the absence or presence of transforming growth factor ß2 stimulation. CONCLUSIONS: Fluorofenidone significantly inhibited expression of SMADs, CTGF, α-SMA, COL-I, and Fn in FHL 124 cells. Due to noncompliance in infants, fluorofenidone may become a novel therapeutic drug against posterior capsular opacification in infants.

Divergent domains of 28S ribosomal RNA gene: DNA barcodes for molecular classification and identification of mites.

BACKGROUND: The morphological and molecular identification of mites is challenging due to the large number of species, the microscopic size of the organisms, diverse phenotypes of the same species, similar morphology of different species and a shortage of molecular data. METHODS: Nine medically important mite species belonging to six families, i.e. Demodex folliculorum, D. brevis, D. canis, D. caprae, Sarcoptes scabiei canis, Psoroptes cuniculi, Dermatophagoides farinae, Cheyletus malaccensis and Ornithonyssus bacoti, were collected and subjected to DNA barcoding. Sequences of cox1, 16S and 12S mtDNA, as well as ITS, 18S and 28S rDNA from mites were retrieved from GenBank and used as candidate genes. Sequence alignment and analysis identified 28S rDNA as the suitable target gene. Subsequently, universal primers of divergent domains were designed for molecular identification of 125 mite samples. Finally, the universality of the divergent domains with high identification efficiency was evaluated in Acari to screen DNA barcodes for mites. RESULTS: Domains D5 (67.65%), D6 (62.71%) and D8 (77.59%) of the 28S rRNA gene had a significantly higher sequencing success rate, compared to domains D2 (19.20%), D3 (20.00%) and D7 (15.12%). The successful divergent domains all matched the closely-related species in GenBank with an identity of 74-100% and a coverage rate of 92-100%. Phylogenetic analysis also supported this result. Moreover, the three divergent domains had their own advantages. D5 had the lowest intraspecies divergence (0-1.26%), D6 had the maximum barcoding gap (10.54%) and the shortest sequence length (192-241 bp), and D8 had the longest indels (241 bp). Further universality analysis showed that the primers of the three divergent domains were suitable for identification across 225 species of 40 families in Acari. CONCLUSIONS: This study confirmed that domains D5, D6 and D8 of 28S rDNA are universal DNA barcodes for molecular classification and identification of mites. 28S rDNA, as a powerful supplement for cox1 mtDNA 5'-end 648-bp fragment, recommended by the International Barcode of Life (IBOL), will provide great potential in molecular identification of mites in future studies because of its universality.

Virtual touch tissue imaging and quantification (VTIQ) in the evaluation of breast lesions: The associated factors leading to misdiagnosis.

PURPOSE: To investigate the factors that could cause a misdiagnosis in virtual touch tissue imaging and quantification (VTIQ) when differentiating benign and malignant breast lesions, and to analyze the imaging characteristics of those lesions with incorrect findings. METHODS: The conventional ultrasound (CUS) features and the VTIQ parameters of 153 benign lesions and 99 malignant lesions were retrospectively analyzed and compared with histopathological and/or core-needle biopsy (CNB)-proven results. Independent variables that led to inaccurate VTIQ results were selected by binary logistic regression analysis. RESULTS: The maximum shear wave speed (SWS-max), the mean SWS (SWS-mean), the minimum SWS (SWS-min), the lesion-to-fat SWS ratio (SWS-L/F), and the lesion-to-gland SWS ratio (SWS-L/G) in malignant lesions were significantly higher than those in benign lesions (all P < 0.001). The false-positive rate (FPR) of benign lesions and the false-negative rate (FNR) of malignant lesions were 9.8% and 19.2%, respectively, using an SWS-max cut-off value of 4.46 m/s. Diameter, depth, and posterior acoustic features were independent variables related to false-positive VTIQ findings (P: 0.049, 0.010 and 0.032, respectively). The invasive status and the histologic grade of infiltrating carcinoma were significantly associated with false-negative VTIQ findings (P: 0.026 and 0.015). CONCLUSION: Diameter, depth, posterior acoustic features, invasive status, and histologic grade have a significant influence on the accuracy of VTIQ results, and these characteristics of breast lesions should be taken into account when interpreting the results of VTIQ examinations.

The function of body coloration of the hai coral snake Sinomicrurus japonicus boettgeri.

BACKGROUND: Prey animals often protect themselves from visual hunting predators via their body coloration, which encompasses various visual effects. When a prey animal displays a certain color pattern on its body surface, its protective function and effect are largely dependent on how a predator would encounter and perceive the prey animal.Asian coral snakes of the genus Sinomicrurus,which are venomous, display black bands and stripes on their orange body coloration. The banded pattern has been characterized as an aposematic signal in the New World coral snakes, but the stripes generally occur in cryptic snakes. We investigated the function of this complex color pattern, which might be interpreted as aposematic and cryptic, in Sinomicrurus japonicusboettgeri. RESULTS: First, plasticine replica experiments were conducted to assess whether natural avian predators avoid the colorpattern of S.japonicus boettgeri;the results showed that they attacked the coral snake replicas and the control replicas with coloration similar to another prey snake, suggesting that the body coloration of S. japonicus boettgeri did not function aposematically in the wild. Second, we evaluated the chromatic contrast of the snake coloration with backgrounds from their natural habitats based on the avian predator visual systems. The body coloration of S. japonicus boettgeri showed the same, or lower, contrast levels with natural backgrounds than those of sympatric cryptic snakes, suggesting that the coloration was ineffective as an aposematic signal. CONCLUSIONS: These results imply that the body coloration of S. japonicus boettgeri would work as crypsis through background matching or disruptive camouflage rather than aposematism.

Effect of quercetin on formation of choroidal neovascularization (CNV) in age-related macular degeneration(AMD).

PURPOSE: Age-related macular degeneration (AMD) as a disease entity is "dry" at early stage and made up of two main components at late stage: atrophic AMD and exudative AMD. Quercetin acts as an anti-oxidant to protect retinal pigment epithelial cells (RPE) from damaged by oxidative stress, but its effect on formation of choroidal neovascularization (CNV) in AMD is unclear. The aim of this study is to investigate the effect of quercetin on the formation of CNV in AMD. METHODS: The development of CNV induced by laser was detected by fluorescein angiography (FA). Colored microsphere technique was used to determine the choroidal blood flow in ocular hypertensive rabbit eyes. In in vitro studies, HUVECs were treated with NaIO3, H2O2 and NaN3 to induce oxidative cell damages. The effect of quercetin on various oxidations-induced injuries in HUVECs was measured by MTT assay. HUVECs migration was assessed using a wound healing assay. RESULTS: Quercetin significantly inhibited the formation of laser-induced CNV. The choroidal blood flow in rabbit eyes was significantly increased after quercetin instillation. In vitro results showed quercetin enhanced various oxidations-induced injuries in HUVECs and inhibited migration of HUVECs during wound healing. CONCLUSION: Quercetin inhibited the formation of CNV both in vivo and in vitro and increased choroidal blood flow. It could become a promising candidate for the treatment of AMD.

Effect of naringenin on NaIO(3)-induced retinal pigment epithelium degeneration and laser-induced choroidal neovascularization in rats.

AIM: To study the effects of naringenin eye drops on NaIO(3)-induced retinal pigment epithelium (RPE) degeneration and laser-induced choroidal neovascularization (CNV) in rat eyes. METHODS: The 35mg/kg NaIO(3)-induced RPE degeneration was prevented by 10g/L naringenin eye drops 3 times a day for 7 days in advance of NaIO(3) injection, and then 2 to 4 weeks thereafter, RPE function was measured with C-wave of electroretinogram (ERG). The laser-induced CNV rats were treated with laser to break the Bruch's membrane and the CNV formation was prevented by 10g/L naringenin eye drops instilled 3 times a day for 2 to 4 weeks. The CNV formation was measured with fluorescein angiography (FA) and flat mount. RESULTS: Two weeks after NaIO(3) injection, the amplitude of ERG C-wave fell markedly in NaIO(3) group to 53% of normal group (P<0.01). No apparent difference was observed in naringenin+NaIO(3) group. Four weeks later, the NaIO(3) group fell to 37% of normal group (P<0.01), while the naringenin+ NaIO(3) group fell to only 57% of normal group (P<0.01). There was a 52% reversal of the ERG C-wave by naringenin as compared to NaIO(3) treated group (P<0.05). Two weeks and four weeks after laser treatment, naringenin reduced the CNV formation to 53% and 49% of control group (100%) measured by FA (P<0.01). Four weeks after laser treatment, naringenin reduced the CNV formation by 47% as compared to control group measured with flat mount (P<0.01). CONCLUSION: Naringenin can significantly protect RPE from NaIO(3) induced degeneration and also prevent CNV formation.

Effect of Tetramethylpyrazine on RPE degeneration, choroidal blood flow and oxidative stress of RPE cells.

AIM: To study the effects of Tetramethylpyrazine (TMP) on retinal pigment epithelium (RPE) degeneration, choroidal blood flow and oxidative stress of RPE cells. METHODS: The 35mg/kg NaIO(3)-induced RPE degeneration rat eyes was given 25µg 1% TMP eye drops 3 times a day for 7 days before NaIO(3) injection, and then 2 to 4 weeks after NaIO(3) injection. RPE function was measured with c-wave of electroretinogram (ERG). Colored microsphere technique was used for in vivo experiments to determine the choroidal blood flow in ocular hypertensive (40mmHg) rabbit eyes. Methylthiazoltetrazolium (MTT) assay was used to study in vitro effect of TMP on various oxidants induced injury in the hRPE (ARPE-19 (ATCC, Manassas, VA, USA)). RESULTS: Two weeks after NaIO(3) injection, the amplitude of ERG c-wave fell markedly in NaIO(3) group to 36% of control group(P<0.01). No apparent difference was observed in TMP+NaIO(3) group. Four weeks later, the NaIO(3) group fell to 46% of control group (P<0.01), while the TMP+NaIO(3) group fell to only 77% of control group (P<0.01). There was a 67% reversal of the ERG c-wave by TMP as compared to NaIO(3) group(P<0.01). The choroidal blood flow was significantly increased at all time points (at 30, 60 and 120 minutes after TMP instillation) as compared with corresponding controls. TMP had no effect on hypoxia-(1% O(2)), t-BHP- and H(2)O(2)-induced damage in RPE cells. 10(g/mL TMP could reverse 1 and 3mM NaN(3)-induced loss of viability of RPE by 18.5% (P<0.01) and 23% (P<0.01), respectively. 30µg/mL TMP could reverse 30 and 100mM NaIO(3) induced loss of viability of RPE by 18.1% (P<0.05) and 16.8% (P<0.01), respectively. CONCLUSION: TMP can significantly protect RPE from NaIO(3) induced degeneration in vivo and oxidative stress in vitro and can increase choroidal blood flow markedly in vivo.

[Practice and experience of the scientific research management].

The practice and experience of the scientific research management in Nanjing General Hospital from 1997 to 2002 is summarized in this review. By presenting the achievement gained in the past 6 years, the author prove to the scientific research managers that the effective manage thought is the key of scientific research management, and also expatriate the experience of the key points management in the management of scientific research subjects.