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Vitamin C (VC) serves as a pivotal nutrient for anti-oxidation process, metabolic responses, and stem cell differentiation. However, its precise contribution to placenta development and gestation remains obscure. Here, we demonstrated that physiological levels of VC act to stabilize Hand1, a key bHLH transcription factor vital for the development trajectory of trophoblast giant cell (TGC) lineages, thereby promoting the differentiation of trophoblast stem cells into TGC. Specifically, VC administration inactivated c-Jun N-terminal kinase (JNK) signaling, which directly phosphorylates Hand1 at Ser48, triggering the proteasomal degradation of Hand1. Conversely, a loss-of-function mutation at Ser48 on Hand1 not only significantly diminished both intrinsic and VC-induced stabilization of Hand1 but also underscored the indispensability of this residue. Noteworthy, the insufficiency of VC led to severe defects in the differentiation of diverse TGC subtypes and the formation of labyrinth's vascular network in rodent placentas, resulting in failure of maintenance of pregnancy. Importantly, VC deficiency, lentiviral knockdown of JNK or overexpression of Hand1 mutants in trophectoderm substantially affected the differentiation of primary and secondary TGC in E8.5 mouse placentas. Thus, these findings uncover the significance of JNK inactivation and consequential stabilization of Hand1 as a hitherto uncharacterized mechanism controlling VC-mediated placentation and perhaps maintenance of pregnancy. [ABSTRACT FROM AUTHOR]

The score profiles could be used to measure learners' skills proficiency via cognitive diagnosis models (CDMs) for predicting their performance in the future examination. The prediction results could provide important decision-making supports for personalized e-learning instruction. However, facing the possible complexity of skills, the uncertainty of learners' skill proficiency and the large-scale volume of score profiles, the existing CDMs have limitations in the measurement mechanisms and diagnostic efficiency. In this paper, we proposed an approach based on a fuzzy cloud cognitive diagnosis framework (FC-CDF) to predicting examinees' performance in e-learning environment. In this approach, the normal cloud models (NCMs) are utilized innovatively to measure the expectation, degree of variation and variation frequency of learners' skill proficiency, and each NCM is transformed into an interval fuzzy number to characterize the uncertainty of the skill proficiency for every learner. Combining the educational psychology hypothesis with the parameter estimation method, we could obtain the learners' skill proficiency level and the slip and guess factors relevant to each test item, based on which the learners' scores could be predicted in a future test. Finally, the experiments demonstrate that the proposed approach provides good accuracy and significantly reduces execution time for predicting examinee performance, compared with the existing methods. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a condition of severe septicemia and septic shock caused by infection, accompanied by multiple organ dysfunction often leading to patients' admission to the intensive care unit (ICU) and death. Objective: This study aims to investigate the efficacy of urinary trypsin inhibitor in the treatment of rats with severe sepsis, and to analyze its effects on coagulation and immunity. Sixty Sprague Dawley rats were randomly divided into a model control group (MCG), an ulinastatin group (UG), and a normal control group (n = 20 each). Rats in the model CG and UG were modeled for severe sepsis through cecal ligation and puncture, and the 72 h survival of the rats in the three groups was recorded. The expression of IL-18 and TNF-α before urinary trypsin inhibitor administration and 72 h after administration was detected by an ELISA. Activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FIB) were determined using a fully automatic coagulation analyzer. CD4 + , CD8 + , and CD4 + /CD8 + levels were quantitated by flow cytometry. Results: After administration, compared with those in the MCG, rats in the UG showed higher survival rates (P < 0.05), lower IL-18 and TNF-α expression (P < 0.05), lower APTT, PT, and TT (P < 0.05), higher FIB (P < 0.05), higher CD4 + and CD4 +/CD8 + levels (P < 0.05), and significantly lower CD8 + levels (P < 0.05). Conclusion: Urinary trypsin inhibitor can increase the survival rate of rats with severe sepsis, reduce their inflammatory responses, and ameliorate coagulation disorders and immune dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the effect of Chlamydia trachomatis (C. trachomatis) on adverse pregnancy outcomes based on the currently available evidence. Methods: Multiple databases were comprehensively searched from the available date of inception through December 9, 2019. The effect of C. trachomatis on adverse pregnancy outcomes was assessed using pooled odds rations (ORs) and 95% confidence intervals (CIs). Egger's test was used for publication bias. Results: Fifty studies involving 502,141 participants were identified. C. trachomatis infection was found to be associated with preterm birth in antibody detection [OR (95% CI): 1.571 (1.112–2.220), P = 0.010] and high-quality assessment [OR (95% CI): 1.734 (1.295–2.321), P < 0.001], preterm premature rupture of membranes (PPROM) in culture detection [OR (95% CI): 4.339 (1.806–10.424), P = 0.001] and high-quality assessment [OR (95% CI): 2.822 (1.333–5.973), P = 0.007], stillbirth [OR (95% CI): 1.585 (1.219–2.062), P = 0.001], low-birthweight babies [OR (95% CI): 2.205 (1.137–4.274), P = 0.019], and babies small for gestational age [OR (95% CI): 1.193 (1.091–1.305), P < 0.001]. No publication bias was exhibited in miscarriage (P = 0.170), preterm birth (P = 0.303), PPROM (P = 0.341), stillbirth (P = 0.533), and low-birthweight babies (P = 0.535). Conclusions: C. trachomatis infection during pregnancy is associated with a higher risk of preterm birth, PPROM, stillbirth, low-birthweight babies, and babies small for gestational age. [ABSTRACT FROM AUTHOR]

Aims: Despite the high economic benefits of using an intensive agriculture system, the sustainable development of Lycium barbarum L. cultivation in Northwest China is hindered by serious negative plant–soil feedback, which may be paralleled by the variation in the microbial rhizosphere community. Methods: Here, we assessed the shift in the bacterial and fungal rhizosphere communities of L. barbarum across a 20-year-old chronosequence of stands at two independent experimental sites in Ningxia, China via real-time PCR and high-throughput sequencing. Results: Stand age significantly influenced the α-diversity and abundance of the fungal rhizosphere community (p < 0.05) but did not affect the bacterial community. Phytopathogenic fungi, including Alternaria, Fusarium, Gibberella, and Stemphylium, were progressively enriched in the rhizosphere as the plant aged. Structure equation model suggested that soil abiotic properties were the direct drivers for bacterial community, whereas stand age and edaphic factor coexplained the succession of the fungal rhizosphere community. Conclusion: Long-term monocropping decoupled plant–bacteria interaction and strengthened the colonization of fungal phytopathogens in L. barbarum rhizosphere. This study presents novel assessments of the links between the shifts in microbial rhizosphere community and the negative plant–soil feedback of L. barbarum. [ABSTRACT FROM AUTHOR]

To pursue high performance for nonenzymatic glucose sensor, fast conversion of redox couple (Ni(OH)↔NiOOH: Ni/Ni) was established on Ni(OH) nanoparticles modified carbon (Ni(OH)/C) composite electrode coupling with concentrated hydroxide electrolyte. The electrode was prepared by in situ precipitation of nano-Ni(OH) on carbon and then treated by cyclic voltammetry. Cyclic voltammetry was also used to identify the extremely high conversion rate of Ni/Ni on the prepared composite electrode. Continuous cyclic voltammetry method with increasing the concentration of glucose on each cycle step by step was employed to promptly determine linear range and appropriate potential for glucose detection in 0.1, 1, and 7 M KOH electrolyte. The amperometric measurement under the optimized condition (0.28 V vs. saturated calomel electrode (SCE) in 7 M KOH) showed that the Ni(OH)/C composite electrode exhibits a sensitivity of 1004.6 μA mM cm in a wide linear range from 1 μM to 15 mM ( R = 0.9999). What is more, favorable selectivity, reproducibility, and stability for glucose detection were also obtained. These performances indicated that the proposed Ni(OH)/C nanocomposite sensor with fast conversion of redox couple is a promising nonenzymatic glucose sensor. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

We present a surface plasmonic resonance sensor composed of Ag strip pairs array embedded in the background material. The calculated results demonstrate that one of the transmission dips of the structure is very sensitive to the background materials. Meanwhile, the structure could achieve the sensitivity (nm/RIU) about 700 nm/RIU, when the slits width of Ag strip pairs is 10 nm. [ABSTRACT FROM AUTHOR]

We adopt a systemic risk indicator measured by the price of insurance against systemic financial distress and assess individual banks' marginal contributions to the systemic risk. The methodology is applied using publicly available data to the 19 bank holding companies covered by the U.S. Supervisory Capital Assessment Program (SCAP), with the systemic risk indicator peaking around $1.1 trillion in March 2009. Our systemic risk contribution measure shows interesting similarity to and divergence from the SCAP loss estimates under stress test scenarios. In general, we find that a bank's contribution to the systemic risk is roughly linear in its default probability but highly nonlinear with respect to institution size and asset correlation. [ABSTRACT FROM AUTHOR]

p53 is the most frequently mutated tumor suppressor gene in human cancer. Recent studies have indicated that p53 mutants not only lose tumor suppression activity but also gain novel oncogenic functions that contribute to tumor malignancy. In this study, we explored mutant p53 as a target for novel anti-cancer treatment in prostate cancer. Using the DU145 human androgen-independent prostate cancer cell line, we show that silencing of mutant p53 gene by RNA interference led to significant inhibition of cell viability and growth, which was associated with cell cycle arrest at G1 and G2/M phase, and ultimately induced massive apoptosis. Mechanistically, p53-siRNA inhibited phosphatidylinositol 3′-kinase/Akt signaling pathway, which might be responsible for the reduced proliferation and apoptosis induction. These findings suggest that RNA interference targeting mutant p53 may serve as a novel therapeutic strategy for the treatment of androgen-independent prostate cancer. [ABSTRACT FROM AUTHOR]

The female genital tract (FGT) harbors very large numbers of bacterial species that are known to play an important role on vaginal health. Previous studies have focused on bacterial diversity in the vagina, but little is known about the ectocervical microbiota associated with FGT infections. In our study, vaginal swabs and ectocervical swabs were collected from 100 participants in China, including 30 women with bacterial vaginosis (BV; BV group), 22 women with cervicitis (Cer group), 18 women with BV in combination with cervicitis (BC group) and 30 healthy control women (CN group). The diversity and richness of cervicovaginal microbiota were investigated with culture-independent polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) and quantitative PCR (qPCR) targeting 11 microorganisms that have been associated with FGT infections. Despite significant interpersonal variations, the PCR-DGGE profiles revealed that vaginal microbiota and ectocervical microbiota were clearly much more complex in the BV group, while the ectocervical microbiota showed no significant difference between healthy and diseased participants. Using species-specific qPCR, BV and cervicitis were significantly associated with a dramatic decrease in Lactobacillus species ( p < 0.05), and potential pathogenic species such as Gardnerella, Atopobium, Eggerthella, Leptotrichia/ Sneathia, and Prevotella were more common and in higher copy numbers in BV than in CN samples ( p values ranged from 0.000 to 0.021). No significant differences were observed between healthy and cervicitis samples ( p > 0.05) in ectocervical microbiota. The total numbers of bacteria were significantly lower in the ectocervix as compared in the vagina ( p < 0.05). Intriguingly, vaginal microbiota from participants with BV in combination with cervicitis was quite different from that of participants with BV or cervicitis alone. Our study demonstrated that the cervicovaginal microbiota was actively involved in the process of FGT infections. The predominant bacteria of the cervicovaginal communities were clearly associated with BV; however, there was not sufficient evidence that the ectocervical microbiota is directly involved in the development of cervicitis. [ABSTRACT FROM AUTHOR]

This paper compares the pricing of credit risk in the bond market and the fast-growing credit default swap (CDS) market. The cointegration test confirms that the theoretical parity relationship between the two credit spreads holds as a long-run equilibrium condition. Nevertheless, substantial deviation from the parity can arise in the short run. The panel data study and the VECM analysis both suggest that the deviation is largely due to the higher responsiveness of CDS premia to changes in credit conditions. Moreover, it exhibits a certain degree of persistence in that only 10% of price discrepancies can be removed within a business day. [ABSTRACT FROM AUTHOR]