Carbon nanotubes integrated photonic barcodes in Herringbone Microfluidics for Multiplex Biomarker Quantification.

Early monitoring of cardiovascular disease (CVD) is crucial for its treatment and prognosis. Hence, highly specific and sensitive detection method is urgently needed. In this study, we propose a novel herringbone microfluid chip with aptamer functionalized core-shell photonic crystal (PhC) barcode integration for high throughput multiplex CVD detection. Based on the PhC derived from co-assembled carboxylated single-wall carbon nanotubes and silicon dioxide nanoparticles, we obtain core-shell PhC barcodes by hydrogel replicating and partially etching. These core-shell PhC barcodes not only retain the original structural colors coding element, but also fully expose a large number of carboxyl elements in the ore for the probe immobilization. We further combine the functionalized barcodes with herringbone groove microfluidic chip to elucidate its acceptability in testing clinical sample. It is demonstrated that the special design of microfluidic chip can significantly enhance fluid vortex resistance and contact frequency, improving the sample capture efficiency and detection sensitivity. These features indicate that our core-shell PhC barcodes-integrated herringbone microfluidic system possesses great potential for multiplex biomarker detection in clinical application.

Efficacy of Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Animal Model of Female Reproductive Diseases: A Meta-Analysis.

BACKGROUND: Female reproductive disorders, such as premature ovarian insufficiency (POI), intrauterine adhesion (IUA) or thin endometrium, and polycystic ovary syndrome (PCOS), are the main factors affecting fertility. Mesenchymal stem cells derived-extracellular vesicles (MSC-EVs) have gained traction as a new potential treatment and were widely studied in these diseases. However, their impact is still not fully clear. METHODS: A systematic search of PubMed, Web of Science, EMBASE, the Chinese National Knowledge of Infrastructure, and WanFang online databases was performed up to September 27th, 2022, and the studies of MSC-EVs-based therapy on the animal models of female reproductive diseases were included. The primary outcomes were anti-Müllerian hormone (AMH) in POI and endometrial thickness in IUA, respectively. RESULTS: 28 studies (POI, N = 15; IUA, N = 13) were included. For POI, MSC-EVs improved AMH at 2 weeks (SMD 3.40, 95% CI 2.02 to 4.77) and 4 weeks (SMD 5.39, 95% CI 3.43 to 7.36) compared with placebo, and no difference was found when compared with MSCs in AMH (SMD -2.03, 95% CI -4.25 to 0.18). For IUA, MSC-EVs treatment could increase the endometrial thickness at 2 weeks (WMD 132.36, 95% CI 118.99 to 145.74), but no improvement was found at 4 weeks (WMD 166.18, 95% CI -21.44 to 353.79). The combination of MSC-EVs with hyaluronic acid or collagen had a better effect on the endometrial thickness (WMD 105.31, 95% CI 85.49 to 125.13) and glands (WMD 8.74, 95% CI 1.34 to 16.15) than MSC-EVs alone. The medium dose of EVs may allow for great benefits in both POI and IUA. CONCLUSIONS: MSC-EVs treatment could improve the functional and structural outcomes in female reproductive disorders. The combination of MSC-EVs with HA or collagen may enhance the effect. These findings can accelerate the translation of MSC-EVs treatment to human clinical trials.

Discovery and Development of a Series of Pyrazolo[3,4-d]pyridazinone Compounds as the Novel Covalent Fibroblast Growth Factor Receptor Inhibitors by the Rational Drug Design.

Alterations of fibroblast growth factor receptors (FGFRs) play key roles in numerous cancer progression and development, which makes FGFRs attractive targets in the cancer therapy. In the present study, based on a newly devised FGFR target-specific scoring function, a novel FGFR inhibitor hit was identified through virtual screening. Hit-to-lead optimization was then performed by integrating molecular docking and site-of-metabolism predictions with an array of in vitro evaluations and X-ray cocrystal structure determination, leading to a covalent FGFR inhibitor 15, which showed a highly selective and potent FGFR inhibition profile. Pharmacokinetic assessment, protein kinase profiling, and hERG inhibition evaluation were also conducted, and they confirmed the value of 15 as a lead for further investigation. Overall, this study exemplifies the importance of the integrative use of computational methods and experimental techniques in drug discovery.

Seasonal and spatial distributions of euphotic zone and long-term variations in water transparency in a clear oligotrophic Lake Fuxian, China.

To assess the seasonal and spatial variations and long-term trends in water optical properties in Lake Fuxian, investigations based on field work in four seasons and a long-term analysis of data from 1980 to 2014 were conducted. The results show that there was no significant variation in the euphotic depth (Zeu) across the four seasons, and no significant correlations between Zeu and potential influencing factors in seasons other than summer, suggesting that the water itself may be a major factor regulating the Zeu in general. Nevertheless, significant differences in Zeu between the north region (NR) and the south region (SR) were observed in all seasonal tests except spring. This finding relates to a higher abundance of chromophoric dissolved organic matter (CDOM) in the NR due to runoff, especially in the rainy seasons (summer and autumn). CDOM and its terrigenous component had an important impact on Zeu in summer, with the highest precipitation, and impacts from suspended solids and non-algal particles were also found in the NR in summer. The Secchi disk depth in the lake decreased clearly over the years, with significantly negative correlations with the increasing permanganate index and air temperature, implying that organic contaminants (CDOM and/or phytoplankton) are important regulators of water transparency. We estimate that the combined effects of climate warming and changes in land use and land cover are also indirect regulating factors. These findings should be considered in the protection of Lake Fuxian, owing to the importance of light penetration in aquatic ecosystems.

Remediation of nitrate-contaminated wastewater using denitrification biofilters with straws of ornamental flowers added as carbon source.

Straws of four ornamental flowers (carnation, rose, lily, and violet) were added into denitrification biofilters using gravel as matrix through vertically installed perforated polyvinylchloride pipes to provide organic carbon for the treatment of nitrate-contaminated wastewater operating in batch mode. Removal efficiencies of nitrate and phosphate, as well as temporal variations of nitrogen and carbon during batches 10 and 19, were investigated and assessed. Nitrate removal was efficiently enhanced by the addition of flower straws, but decreased gradually as the organic substances were consumed. Phosphate removal was also improved, although this very limited. High nitrate removal rates were achieved during the initial 12 h in the two batches each lasting for 3 days, along with the depletion of influent dissolved oxygen due to aerobic degradation of the organic compounds. NO2(-)-N of 0.01-2.83 mg/L and NH4(+)-N of 0.02-1.69 mg/L were formed and both positively correlated to the nitrate reduced. Inorganic carbon (IC) concentrations increased during the batches and varied conversely with the nitrate contents, and could be indicative of nitrate removal due to the highly significant positive correlation between NO3(-)-N removed and IC concentration (r(2) = 0.881, p < 0.0001). It is feasible and economical to use the denitrification biofilter to treat nitrate-contaminated wastewater, although further optimization of carbon source addition is still required.

Repeated medical abortions and the risk of preterm birth in the subsequent pregnancy.

PURPOSE: The aim of this study was to determine the impact of repeated first trimester mifepristone-induced medical abortions on the risk of preterm birth in a subsequent pregnancy. METHODS: This is a pregnancy-based cohort study. Clinical data were collected from seven public hospitals in Chengdu, China from January 2006 to December 2009. Pregnant women with one or more first trimester mifepristone-induced medical abortions, and/or one or more surgical abortions, or no previous induced abortions were included in the study. The women were monitored through pregnancy and birth. Samples for analysis included 18,024 singleton births. RESULTS: The risk of preterm birth among women with one or more first trimester mifepristone-induced abortions did not differ significantly from the risk among primigravida women (OR 1.03, 95% confidence interval 0.53-1.63). The risks of preterm birth were higher among women with repeated surgical abortions in comparison to women with repeated medical abortions (OR 1.22, 95% confidence interval 1.03-1.64). CONCLUSIONS: A history of multiple first trimester mifepristone-induced abortions is not associated with a higher risk of preterm delivery among singleton births in the first subsequent pregnancy.

[Trends of maternal mortality ratio during 1996-2010 in China].

OBJECTIVE: To analyze time trend and regional disparities in maternal mortality ratio (MMR) and major causes of maternal death in China from 1996 to 2010. METHODS: Data used in this study were based on national maternal mortality surveillance system. From 1996 to 2005, it included 176 monitoring districts (countries) in 31 provinces, autonomous regions and municipalities in the inner land. From 2006 to the present, it covered 336 districts (countries). MMR, major causes of maternal death and their reduction margin, average annual reduction rate in different times and regions from 1996 to 2010 were analyzed. The trend and regional differences in MMRs and major causes of mortality were analyzed using Cochran-Armitage trend and Poisson Test. RESULTS: From 1996 to 2010, Chinese MMR has decreased by 53.2% from 64.7 in 1996 to 30.0 per 100 000 live births in 2010. MMR was higher in rural areas (30.1/100 000) than in urban areas (29.7/100 000), and highest in the west region (46.1/100 000) followed by the middle region (29.1/100 000) and the east region (17.8/100 000) in 2010. MMR in east, middle and west regions have decreased by 37.76%, 57.02% and 66.27% respectively from 1996 to 2010. The disparities between different regions were decreasing. From 2006 to 2010, MMR in rural areas has dropped to 1.82 times of the city, and that in the west was 3 times of the east. Obstetric hemorrhage was still the leading cause of maternal death, responsible for 47.9% maternal deaths in 1996 and 27.8% in 2010. The risk of death due to obstetric hemorrhage was decreasing. CONCLUSION: The MMR in China showed the decreasing trends. Although the regional disparities were still remarkable, they demonstrated narrowing trends. Interventions on maternal death should be focused in rural areas and west regions.

[Influence of dexamethasone on expression of 11beta-HSD2 in primary cultured cytotrophoblasts from human preterm placenta].

OBJECTIVE: To study the influence of dexamethasone (DEX) on the expression of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in primary cultured cytotrophoblasts from human preterm placenta. METHODS: Placenta villous cytotrophoblasts from preterm birth were cultured with the protocol of enzymatic dissociation and tissue incubation method. After isolation and identification, cytotrophoblasts were treated with the repeated administration of DEX (100 nmol/L), or DEX-RU486 (1 micromol/L) for 7 days, in which DEX was not added into the culture at 4th day. Cytotrophoblasts were collected everyday, and the expression levels of 11beta-HSD2 mRNA and protein were determined by real-time fluorescence quantitative PCR and Western blot method. RESULTS: After the treatment of DEX (100 nmol/L), the expression of 11beta-HSD2 mRNA and protein in cytotrophoblast increased in the first three days (P < 0.05). At 4th day, 11beta-HSD2 mRNA and protein declined in the absence of DEX. In 5th-7th day, the increase of 11beta-HSD2 expression were resumed when cytotrophoblasts received DEX again (P < 0.05). With the treatment of DEX and RU486 (l micromol/L), both mRNA and protein level of 11beta-HSD2 in cytotrophoblasts were lower than those with DEX alone, but there was not significantly different (P > 0.05). CONCLUSION: Repeated administration of DEX can upregulate the expression level of 11beta-HSD2 in primary cultured cytotrophoblasts from preterm placenta. Cytotrophoblasts from preterm birth may have the ability to protect the infants by the mechanism of 11beta-HSD2 regulation.