Study on the Relationship and Predictive Value of First-Trimester Pregnancy-Associated Plasma Protein-A, Maternal Factors, and Biochemical Parameters in Gestational Diabetes Mellitus: A Large Case-Control Study in Southern China Mothers.

Objective: To investigate the relationship and predictive value of first-trimester pregnancy-associated plasma protein A (PAPP-A), maternal factors, and biochemical parameters with gestational diabetes mellitus (GDM) in southern China mothers. Methods: This study recruited 4872 pregnant women. PAPP-A, the free beta subunit of human chorionic gonadotropin (free ß-HCG), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), and high- and low-density lipoproteins (HDL, LDL) were measured at 11-13+ weeks of gestation. GDM was diagnosed based on a 75 g oral glucose tolerance test at 24-28 weeks of gestation. We performed stepwise logistic regression analysis to determine the odds ratio (OR) and the 95% confidence interval (CI) of GDM. We used Receiver Operating Characteristic (ROC) curves with the area under the curve (AUC) to evaluate the predictive value of PAPP-A, maternal factors, and biochemical markers. The significance of the differences between the AUC values was assessed using the DeLong test. Results: GDM was diagnosed in 750 (15.39%) women. Independent factors for GDM were age, pre-gestational BMI, GWG before a diagnosis of GDM, previous history of GDM, family history of diabetes, FPG, TG, LDL, PAPP-A, and TC. The AUC of PAPP-A was 0.56 (95% CI 0.53-0.58). The AUC of a model based on combined maternal factors, biochemical markers, and PAPP-A was 0.70 (95% CI 0.68-0.72). Differences in AUC values between PAPP-A alone and the model based on combined maternal factors, biochemical markers, and PAPP-A were statistically significant (Z= 9.983, P<0.001). Conclusion: A Low serum PAPP-A level in the first trimester is an independent risk factor for developing GDM later in pregnancy. However, it is not a good independent predictor although the predictive value of a low serum PAPP-A level increases when combined with maternal factors and biochemical markers.

Portable Paper-Based Nucleic Acid Enrichment for Field Testing.

Point-of-care testing (POCT) can be the method of choice for detecting infectious pathogens; these pathogens are responsible for not only infectious diseases such as COVID-19, but also for certain types of cancers. For example, infections by human papillomavirus (HPV) or Helicobacter pylori (H. pylori) are the main cause of cervical and stomach cancers, respectively. COVID-19 and many cancers are treatable with early diagnoses using POCT. A variety of nucleic acid testing have been developed for use in resource-limited environments. However, questions like unintegrated nucleic acid extraction, open detection systems increase the risk of cross-contamination, and dependence on expensive equipment and alternating current (AC) power supply, significantly limit the application of POCT, especially for on-site testing. In this paper, a simple portable platform is reported capable of rapid sample-to-answer testing within 30 min based on recombinase polymerase amplification (RPA) at a lower temperature, to detect SARS-CoV-2 virus and H. pylori bacteria with a limit of detection as low as 4 × 102 copies mL-1 . The platform used a battery-powered portable reader for on-chip one-pot amplification and fluorescence detection, and can test for multiple (up to four) infectious pathogens simultaneously. This platform can provide an alternative method for fast and reliable on-site diagnostic testing.

CHDbase: A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations.

Congenital heart disease (CHD) is one of themost common causes of major birth defects, with a prevalence of 1%. Although an increasing number of studies have reported the etiology of CHD, the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice. We therefore developed CHDbase, an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications, linking 1124susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes. Metadata such as the information of each publication and the selected population and samples, the strategy of studies, and the major findings of studies were integrated with each item of the research record. We also integrated functional annotations through parsing ∼ 50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity. We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes. The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin. Overall, CHDbase provides a comprehensive and freely available resource to study CHD susceptibilities, supporting a wide range of users in the scientific and medical communities. CHDbase is accessible at http://chddb.fwgenetics.org.

Association between isolated maternal hypothyroxinemia during the first trimester and adverse pregnancy outcomes in Southern Chinese women: a retrospective study of 7051 cases.

BACKGROUND: The association between isolated maternal hypothyroxinemia (IMH) and adverse pregnancy outcomes is still controversial. This study aimed to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes in southern Chinese women. METHODS: This was a hospital-based, retrospective cohort study. The records of 7051 women, including 1337 IMH women and 5714 euthyroid women who had a singleton pregnancy and accepted routine prenatal service at the Third Affiliated Hospital of Sun Yat-Sen University from January 2015 to September 2018, were extracted from the electronic medical records system in this study. Thyroid functions [thyroid-stimulating hormone (TSH), free thyroxine (fT4) and anti-thyroperoxidase autoantibody (TPO-Ab)] had to be measured before 13 weeks and 6 days of gestation. The chi-square test and multivariate logistic regression analysis were applied to evaluate the association between IMH during the first trimester and adverse pregnancy outcomes. RESULTS: Prepregnancy obesity [prepregnancy body mass index (preBMI) ≥ 25 kg/m2] was found to be more common in the IMH group (11.2% vs. 6.1%) (P < 0.05). The prevalence of gestational diabetes mellitus (GDM), postpartum haemorrhage (PPH), macrosomia and large for gestational age (LGA) was higher in the IMH group. However, after using multivariate logistic regression analysis to adjust for confounders (maternal age, educational levels and preBMI), only LGA was shown to be associated with an increased risk in IMH women [adjusted OR: 1.27 (95% CI 1.044-1.566)]. The prevalence of preterm delivery (either < 37 or < 34 weeks), gestational hypertension, preeclampsia, placenta previa, placental abruption, premature rupture of membrane (PROM), intrauterine growth restriction (IUGR), polyhydramnios, stillbirth, small for gestational age (SGA) and low Apgar score did not increase. CONCLUSION: IMH during the first trimester did not increase any risk of adverse pregnancy outcomes in southern Chinese women except LGA.

Impact of Early Pregnancy Subclinical Hypothyroidism on Gestational Diabetes Mellitus: A Retrospective Study of 7,536 Cases.

Background: Maternal subclinical hypothyroidism (SCH) has been associated with adverse pregnancy outcomes. This study aimed to explore whether SCH in the first trimester contributed to the development of gestational diabetes mellitus (GDM). Materials and Methods: A total of 8,777 pregnant women who first visited before 13 weeks and 6 days of gestation and accepted routine prenatal service at the Third Affiliated Hospital of Sun Yat-Sen University from January 2015 to September 2018 were recruited in this study. Thyroid functions (thyroid stimulating hormone [TSH], free T4, and thyroid peroxidase antibody [TPOAb]) were measured before 13 weeks and 6 days of gestation and data of 7,536 subjects with TSH ≥0.1 mIU/L were analyzed. A 2-hour 75-g oral glucose tolerance test was performed between 24 and 28 gestational weeks. Chi-square test and multivariate logistic regression analysis were applied to evaluate the relationship between SCH and GDM. Results: The prevalence of SCH in this population was 7.53%. After stratifying the relationship between SCH and GDM according to TSH concentrations (slightly elevated TSH: ≥2.5, <4.0 mIU/L; moderately elevated TSH: ≥4.0, <10.0 mIU/L) and TPOAb status, a moderately elevated TSH combined with positive TPOAb (23.9% vs. normal 13.0%, chi-square = 6.317, p = 0.012) was found to increase the incidence of GDM. Furthermore, after adjusting for confounders (maternal age, educational levels, parity, and pregestational body mass index [preBMI]), the SCH group still exhibited a higher risk of GDM (relative risk [RR] 1.867, 95% confidence interval [CI] 1.018-3.424). Conclusion: Our findings indicated that SCH during early pregnancy, in the presence of moderately elevated TSH levels and positive TPOAb, might lead to an increased risk of GDM.

Evaluation of association studies and a systematic review and meta-analysis of VDR polymorphisms in type 2 diabetes mellitus risk.

ABSTRACT: Numerous original studies and 4 published meta-analyses have reported the association between the Vitamin D receptor (VDR) BsmI, FokI, ApaI, and TaqI polymorphisms and type 2 diabetes mellitus (T2DM) risk. However, the results were inconsistent. Therefore, an updated meta-analysis was performed to further explore these issues.To further explore the association between the VDR BsmI, FokI, ApaI, and TaqI polymorphisms and T2DM risk.PubMed, EMBASE, Scopus, and Wanfang databases were searched. The following search strategy were used: (VDR OR vitamin D receptor) AND (polymorphism OR variant OR mutation) AND (diabetes OR mellitus OR diabetes mellitus). Pooled crude odds ratios with 95% confidence intervals were applied to evaluate the strength of association in 5 genetic models. Statistical heterogeneity, the test of publication bias, and sensitivity analysis were carried out using the STATA software (Version 12.0). To evaluate the credibility of statistically significant associations, we applied the false-positive report probabilities (FPRP) and Bayesian false discovery probability (BFDP) test.Overall, the VDR BsmI polymorphism was associated with a significantly decreased T2DM risk in Asians; the VDR FokI polymorphism was associated with a significantly decreased T2DM risk in Asians, African countries, and Asian countries; the VDR ApaI polymorphism was associated with a significantly decreased T2DM risk in Caucasians and North American countries.On the VDR ApaI polymorphism, a significantly increased T2DM risk was found in a mixed population. However, when we further performed a sensitivity analysis, FPRP, and BFDP test, less-credible positive results were identified (all FPRP > 0.2 and BFDP > 0.8) in any significant association.In summary, this study strongly indicates that all significant associations were less credible positive results, rather than from true associations.

MiR-101-containing extracellular vesicles bind to BRD4 and enhance proliferation and migration of trophoblasts in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a frequently occurring pregnancy disorder in the placenta, which results in various maternal and fetal complications. The current study aims to evaluate the role of extracellular vesicles (EVs)-encapsulated microRNA (miR)-101 in biological processes of trophoblasts in PE and its underlying mechanism. METHODS: Human umbilical cord mesenchymal stem cell (HUCMSC) and HUCMSC-derived EVs were isolated and cultured, after which EV characterization was carried out using PKH67 staining. In silico analyses were adopted to predict the downstream target genes of miR-101, and dual luciferase reporter gene assay was applied to validate the binding affinity. Furthermore, loss- and gain-of-function approaches were adopted to determine the role of miR-101 and bromodomain-containing protein 4 (BRD4) in trophoblast proliferation and invasion using EDU staining and transwell assay. In addition, a rat model of PE was established to verify the function of EV-encapsulated miR-101 in vivo. RESULTS: Placental tissues obtained from PE patients presented with downregulated miR-101 expression and upregulated BRD4 and CXCL11 expression. EV-encapsulated miR-101 from HUCMSCs could be delivered into the trophoblast HTR-8/SVneo cells, thus enhancing proliferation and migration of trophoblasts. Mechanically, miR-101 targeted and negatively regulated BRD4 expression. BRD4 knockdown promoted the proliferation and migration of trophoblasts by suppressing NF-κB/CXCL11 axis. EV-encapsulated miR-101 from HUCMSCs also reduced blood pressure and 24 h urine protein in vivo, thereby ameliorating PE. CONCLUSION: In summary, EV-encapsulated miR-101 promoted proliferation and migration of placental trophoblasts through the inhibition of BRD4 expression via NF-κB/CXCL11 inactivation.

An ultraportable and versatile point-of-care DNA testing platform.

Point-of-care testing (POCT) has broad applications in resource-limited settings. Here, a POCT platform termed POCKET (point-of-care kit for the entire test) is demonstrated that is ultraportable and versatile for analyzing multiple types of DNA in different fields in a sample-to-answer manner. The POCKET is less than 100 g and smaller than 25 cm in length. The kit consists of an integrated chip (i-chip) and a foldable box (f-box). The i-chip integrates the sample preparation with a previously unidentified, triple signal amplification. The f-box uses a smartphone as a heater, a signal detector, and a result readout. We detected different types of DNA from clinics to environment to food to agriculture. The detection is sensitive (<103 copies/ml), specific (single-base differentiation), speedy (<2 hours), and stable (>10 weeks shelf life). This inexpensive, ultraportable POCKET platform may become a versatile sample-to-answer platform for clinical diagnostics, food safety, agricultural protection, and environmental monitoring.

Transformation of Biomass DNA into Biodegradable Materials from Gels to Plastics for Reducing Petrochemical Consumption.

Ancient biomass is the main source for petrochemicals including plastics, which are inherently difficult to be degraded, increasingly polluting the earth's ecosystem including our oceans. To reduce the consumption by substituting or even replacing most of the petrochemicals with degradable and renewable materials is inevitable and urgent for a sustainable future. We report here a unique strategy to directly convert biomass DNA, at a large scale and with low cost, to diverse materials including gels, membranes, and plastics without breaking down DNA first into building blocks and without polymer syntheses. With excellent and sometimes unexpected, useful properties, we applied these biomass DNA materials for versatile applications for drug delivery, unusual adhesion, multifunctional composites, patterning, and everyday plastic objects. We also achieved cell-free protein production that had not been possible by petrochemical-based products. We expect our biomass DNA conversion approach to be adaptable to other biomass molecules including biomass proteins. We envision a promising and exciting era coming where biomass may replace petrochemicals for most if not all petro-based products.

A PEGDA/DNA Hybrid Hydrogel for Cell-Free Protein Synthesis.

Cell-free protein synthesis (CFPS) has the advantage of rapid expression of proteins and has been widely implemented in synthetic biology and protein engineering. However, the critical problem limiting CFPS industrial application is its relatively high cost, which partly attributes to the overexpense of single-use DNA templates. Hydrogels provide a possible solution because they can preserve and reutilize the DNA templates in CFPS and have great potential in elevating the protein production yield of the CFPS. Here, we presented a low-cost hybrid hydrogel simply prepared with polyethylene glycol diacrylate (PEGDA) and DNA, which is capable of high-efficient and repeated protein synthesis in CFPS. Parameters governing protein production specific to hybrid hydrogels were optimized. Structures and physical properties of the hybrid hydrogel were characterized. Transcription and expression kinetics of solution phase system and gel phased systems were investigated. The results showed that PEGDA/DNA hydrogel can enhance the protein expression of the CFPS system and enable a repeated protein production for tens of times. This PEGDA/DNA hybrid hydrogel can serve as a recyclable gene carrier for either batch or continuous protein expression, and paves a path toward more powerful, scalable protein production and cell-free synthetic biology.

Utility of MELD scoring system for assessing the prognosis of acute fatty liver of pregnancy.

OBJECTIVE: To evaluate the value of Model for end-stage liver disease (MELD) in assessing the prognosis of acute fatty liver of pregnancy (AFLP). STUDY DESIGN: This was a retrospective study. From January 2010 to July 2018, data of 53 women diagnosed with AFLP in the third affiliated hospital of Sun Yat-Sen University were collected. Blood samples were collected on admission and MELD score was calculated. The MELD score was calculated by using the original MELD formula as shown: 9.57 log (creatinine) + 3.78 log (bilirubin) + 11.20 log (international normalized ratio, INR) + 6.43. The perinatal outcomes were documented. RESULTS: Nine women were excluded as they were transfered to our hospital after delivery in other hospitals. The remaining 44 women had average age of 28.8 ±â€¯5.2 years. The MELD score showed good performance in predicting most of the perinatal complications of AFLP with all the area under the receiver operating characteristic (ROC) curves (AUC) > 0.8, including ascites (AUC: 0.91, 95% CI: 0.78-0.98), wound seroma (AUC: 0.91, 95% CI: 0.78-0.93), hepatic encephalopathy (AUC: 0.93, 95% CI: 0.82-0.99), DIC (AUC: 0.87, 95% CI: 0.74-0.95), sepsis (AUC: 0.93, 95% CI: 0.82-0.99), renal insufficiency (AUC: 0.94, 95% CI: 0.82-0.99) and stillbirth (AUC: 0.85, 95% CI: 0.71-0.94). Nearly all the maternal complications were more frequently happened in MELD score ≥30 group (P < 0.05). CONCLUSION: MELD scoring system may be a suitable method for assessing the prognosis of AFLP.

First-trimester fasting plasma glucose as a predictor of gestational diabetes mellitus and the association with adverse pregnancy outcomes.

OBJECTIVE: To evaluate the usefulness of a fasting plasma glucose (FPG) at the first trimester in predicting gestational diabetes mellitus (GDM) and the association between FPG and adverse pregnancy outcomes. METHODS: The levels of FPG in women with singleton pregnancies were measured at 9-13+6 weeks. A two hour 75-g oral glucose tolerance test (OGTT) was completed at 24-28 weeks and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria was used. Adverse pregnancy outcomes were assessed and recorded. RESULTS: Among 2112 pregnant women enrolled in the study, 224 (10.6%) subjects were diagnosed with GDM. The AUC for FPG in predicting GDM was 0.63 (95% CI 0.61- 0.65) and the optimal cutoff value was 4.5 mmol/L (sensitivity 64.29% and specificity 56.45%). Higher first-trimester FPG increased the prevalence of GDM, large for gestational age (LGA) and assisted vaginal delivery and/or cesarean section (all P < 0.05). CONCLUSION: FPG at first trimester could be used to predict GDM and higher first-trimester FPG was associated with adverse pregnancy outcomes.

Effect of mildly elevated thyroid-stimulating hormone during the first trimester on adverse pregnancy outcomes.

BACKGROUND: To investigate the effect of a mildly elevated thyroid-stimulating hormone (TSH) concentration between 2.5 and 4.0 mIU/L during the first trimester on pregnancy outcomes in thyroid peroxydase antibody (TPOAb)-negative pregnant women. METHODS: A total of 1858 pregnant women who were TPOAb-negative before 13+ 6 gestational weeks, received regular prenatal services, and delivered in the third affiliated hospital of Sun Yat-Sen University were recruited from June 2016 to June 2017. Measurements of thyroid function (TSH, free T4 [FT4] and TPOAb) and adverse pregnancy outcomes were assessed and recorded. RESULTS: Among the 1858 study participants, the 97.5th percentile for TSH was 3.76 mIU/L, and 142 women (7.6%) had mildly elevated TSH levels between 2.5 and 4.0 mIU/L. No differences in the incidence of adverse pregnancy outcomes were observed between patients with a mildly elevated TSH level and those with a normal TSH level (< 2.5 mIU/L). CONCLUSION: A mildly elevated TSH concentration (2.5-4.0 mIU/L) during the first trimester of pregnancy in TPOAb-negative women was not associated with adverse pregnancy outcomes in our study population. Accordingly, it may be possible to raise the upper limit of the healthy TSH reference range for pregnant women.

First Trimester Neck Circumference as a Predictor for the Development of Gestational Diabetes Mellitus.

BACKGROUNDS: This study aimed to evaluate the relationship between neck circumference (NC) and gestational diabetes mellitus (GDM), and the efficacy of NC in predicting GDM by comparing with pregestational body mass index (preBMI) in southern Chinese woman. MARERIALS AND METHODS: A total of 371 pregnant women (97 GDM and 274 normal pregnant women) were recruited from the third affiliated hospital of Sun Yat-Sen University, Guangzhou, China. NC was measured at 11-13+6 gestational weeks. GDM was diagnosed through a 75-g oral glucose tolerance test at 24-28 gestational weeks. Using the receiver-operator characteristic (ROC) curve analysis, we evaluated the association between NC and GDM. RESULTS: The area under the receiver operator characteristic curves were 0.65 (95% CI: 0.60-0.70) for NC and 0.64 (95% CI: 0.59-0.69) for preBMI in diagnosing GDM and no difference was found between them (P = 0.66). NC ≥ 33.8cm was determined to be the best cut-off level for identifying subjects with GDM (sensitivity 68.04% and specificity 59.12%). Multivariate logistic regression analysis showed that a large NC in the first trimester was an independent risk factor for the development of GDM (odds ratio [OR] = 1.29, 95% CI: 1.72-7.45). CONCLUSIONS: NC, as well as preBMI, might be a novel anthropometric index for GDM screening. The increase of NC could be an independent risk factor for GDM in first trimester pregnancy.

Pollen magnetofection for genetic modification with magnetic nanoparticles as gene carriers.

Genetic modification plays a vital role in breeding new crops with excellent traits. Almost all the current genetic modification methods require regeneration from tissue culture, involving complicated, long and laborious processes. In particular, many crop species such as cotton are difficult to regenerate. Here, we report a novel transformation platform technology, pollen magnetofection, to directly produce transgenic seeds without regeneration. In this system, exogenous DNA loaded with magnetic nanoparticles was delivered into pollen in the presence of a magnetic field. Through pollination with magnetofected pollen, transgenic plants were successfully generated from transformed seeds. Exogenous DNA was successfully integrated into the genome, effectively expressed and stably inherited in the offspring. Our system is culture-free and genotype independent. In addition, it is simple, fast and capable of multi-gene transformation. We envision that pollen magnetofection can transform almost all crops, greatly facilitating breeding processes of new varieties of transgenic crops.

Cr:ZnS saturable absorber passively Q-switched mode-locking Tm,Ho:LLF laser.

We first report on a diode-end-pumped passively Q-switched mode-locking Tm,Ho:LLF laser at 2053 nm by using a Cr:ZnS saturable absorber. A stable Q-switched mode-locking pulse train with a nearly 100% modulation depth was achieved. The repetition frequency of the Q-switched pulse envelope increased from 0.5 to 12.3 kHz with increasing pump power from 1 to 4.36 W. The maximum average output power of 145 mW was obtained, and the width of the mode-locked pulse was estimated to be less than 682 ps with a 250 MHz repetition frequency within a Q-switched pulse envelope of about 700 ns.

Utility of Pregestational Body Mass Index and Initial Fasting Plasma Glucose in Predicting Gestational Diabetes Mellitus.

OBJECTIVE: The present study aimed to evaluate the pregestational body mass index (preBMI) and initial fasting plasma glucose (FPG) in predicting gestational diabetes mellitus (GDM) in southern Chinese women. STUDY DESIGN: A total of 327 pregnant women were recruited from the third affiliated hospital of Sun Yat-Sen University, Guangzhou, China. The preBMI and initial FPG at 16-18 weeks' gestation were measured. Oral glucose tolerance test was performed at 24-28 weeks' gestation. The sensitivity and specificity of preBMI and initial FPG as predictors for GDM were evaluated by receiver-operator characteristic curve analysis. RESULTS: Both preBMI and initial FPG correlated with the 0-hour, 1-hour and 2-hour plasma glucose during oral glucose tolerance test (P < 0.05). The area under receiver-operator characteristic curve was 0.63 (95% CI: 0.57-0.68) for preBMI and 0.68 (95% CI: 0.61-0.72) for initial FPG in diagnosing GDM. The optimal cutoff for preBMI was 21.5 kg/m(2) (sensitivity 52.1% and specificity 69.2%) and 4.6 mmol/L (sensitivity 64.6% and specificity 65.2%) for initial FPG. Interestingly, the initial FPG had a better sensitivity compared to preBMI when the specificity was the same. Multivariate logistic regression analysis showed that initial FPG but not preBMI was the independent risk factor for the later development of GDM. After adjustment for the preBMI and the maternal age, the odds ratios of initial FPG and parity were 3.57 (95% CI: 1.72-7.45) and 2.11 (95% CI: 1.20-3.72). CONCLUSIONS: Although both preBMI and initial FPG could be used as indicators for GDM, the initial FPG may be more suitable for predicting GDM in southern Chinese women.

Characterization and Insights Into the Nano Liposomal Magnetic Gene Vector Used for Cell Co-Transfection.

The development of magnetofection technology has brought a promising method for gene delivery. Here, we develop a novel liposomal magnetofection system, consisted of magnetic nanoparticle and liposome through molecular assembly, was applied to introduce double genes into porcin somatic cells with high co-transfection efficiency. The performace of liposomal magnetic gene nanovectors has been evaluated by involving the micro morphology, diameters distribution, zeta potentials and the capacity of loading DNA molecules. The assembly way among magnetic gene nanovectors and DNA molecules was investigated by atomic force microscopy. Liposomal nano magnetic gene vectors complexes displayed nanoscale assembly and formed compact "fishing-net structure" after combining with plasmid DNA, which is favorable to enhance the loading capacity of DNA molecules.

Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans.

Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi-drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections.

[Construction and characterization of liposomal magnetofection system in pig kidney cells].

Magnetic nano gene vector is one of the non-viral gene vectors, modified by functional group to bind cationic transfect reagents. Coupling magnetofection with the universal lipofection we developed a novel somatic cell transfection method as the so-called liposomal magnetofection (LMF). This approach is potential to provide somatic cell cloning with stable genetic cell lines to cultivate transgenic animals. In order to construct such liposomal magnetic gene vectors complexes system, we used nano magnetic gene vector to combine with liposomal cationic transfect reagents by molecular self-assembly. This vectors system successfully carried exogenous gene and then transfected animal somatic cells. Here, we conducted atomic force microscopy (AFM), zeta potential-diameter analysis and other characterization experiments to investegate the size distribution and morphology of magnetic nanoparticles, the way of the vectors to load and concentrate DNA molecules. Our data reveal that, the LMF of Pig Kidney cells exhibited higher transfection efficiency comparing with the transfection mediated by the commercial lipofectamine2000. Moreover, LMF method overcomes the constraint of transient expression mediated by lipofection. Meanwhile, MTT assay showed low cytotoxicity of LMF. Hence, LMF is a feasible, low cytotoxic and effective method of cell transfection.