Kinetics and Mechanism Study of Competitive Inhibition of Jack-Bean Urease by Baicalin

Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC50 of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of Ki=3.89 × 10−3 mM was followed by a slow isomerization into the final complex with an overall inhibition constant of Ki*=1.47×10-4 mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases

Analysis of Travel Hot Spots of Taxi Passengers Based on Community Detection

It is an important content of smart city research to study the activity track of urban residents, dig out the hot spot areas and spatial interaction patterns of different residents’ activities, and clearly understand the travel rules of urban residents' activities. This study used community detection to analyze taxi passengers’ travel hot spots based on taxi pick-up and drop-off data, combined with multisource information such as land use, in the main urban area of Nanjing. The study revealed that, for the purpose of travel, the modularity and anisotropy rate of the community where the passengers were picked up and dropped off were positively correlated during the morning and evening peak hours and negatively correlated at other times. Depending on the community structure, pick-up and drop-off points reached significant aggregation within the community, and interactions among the communities were also revealed. Based on the type of land use, as passengers' travel activity increased, travel hot spots formed clusters in urban spaces. After comparative verification, the results of this study were found to be accurate and reliable and can provide a reference for urban planning and traffic management

Brief Report: Immune Microenvironment Determines the Immunogenicity of Induced Pluripotent Stem Cell Derivatives.

International audienceThe breakthrough of induced pluripotent stem cells (iPSCs) has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. However, the immunogenicity of iPSC-derived cells remains controversial. Using syngeneic C57BL/6 (B6) mouse transplantation model, several studies indicate that B6 iPSC-derived cells exhibit some levels of immunogenicity when transplanted into B6 mice subcutaneously. In contrast, one recent study has concluded that various lineages of B6 iPSC-derived cells exhibit no immunogenicity when transplanted under the kidney capsule of B6 mice. To resolve the controversy concerning this critical issue of iPSC biology, we used the same B6 transplantation model to demonstrate that the immune response toward antigens is dependent on the immune environment of the transplantation site. Immunogenic antigen-expressing B6 embryonic stem cells (ESCs) as well as B6 iPSCs and their terminally differentiated cells survived under the kidney capsule but are immune rejected when transplanted subcutaneously or intramuscularly. The cotransplantation of mature B6 dendritic cells under the kidney capsule leads to immune rejection of B6 iPSC-derived grafts but not B6 ESC-derived grafts, indicating that the lack of detectable immune response to iPSC-derived grafts under the kidney capsule is due to the lack of functional antigen presenting cells

Brief Report: Immune Microenvironment Determines the Immunogenicity of Induced Pluripotent Stem Cell Derivatives.

International audienceThe breakthrough of induced pluripotent stem cells (iPSCs) has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. However, the immunogenicity of iPSC-derived cells remains controversial. Using syngeneic C57BL/6 (B6) mouse transplantation model, several studies indicate that B6 iPSC-derived cells exhibit some levels of immunogenicity when transplanted into B6 mice subcutaneously. In contrast, one recent study has concluded that various lineages of B6 iPSC-derived cells exhibit no immunogenicity when transplanted under the kidney capsule of B6 mice. To resolve the controversy concerning this critical issue of iPSC biology, we used the same B6 transplantation model to demonstrate that the immune response toward antigens is dependent on the immune environment of the transplantation site. Immunogenic antigen-expressing B6 embryonic stem cells (ESCs) as well as B6 iPSCs and their terminally differentiated cells survived under the kidney capsule but are immune rejected when transplanted subcutaneously or intramuscularly. The cotransplantation of mature B6 dendritic cells under the kidney capsule leads to immune rejection of B6 iPSC-derived grafts but not B6 ESC-derived grafts, indicating that the lack of detectable immune response to iPSC-derived grafts under the kidney capsule is due to the lack of functional antigen presenting cells

Minimally invasive surgery for gynecological cancers: Experience of one institution

Objective: Minimally invasive techniques are increasingly used in gynecological cancer surgery. Although many studies worldwide have looked at the safety and outcomes of the laparoscopic approach to gynecological cancers, there is a lack of data on this subject in our local setting. We therefore reviewed the safety and morbidity of laparoscopic techniques for gynecological cancers in Singapore's largest gynecological cancer center. Methods: We carried out a retrospective review of a prospectively maintained database of all patients from Kerdang Kerbau Women's and Children's Hospital who underwent laparoscopic staging surgery for gynecological cancers over a 5-year period from January 2008 to December 2012. We obtained information on patient demographics, the clinical–pathological features, and perioperative and follow-up details, including intraoperative and postoperative complication rates, from clinical notes and electronic records. Results: In total, 142 patients were included in the study. Ninety-eight patients underwent full staging surgery for endometrial cancer and 44 patients underwent full staging surgery for cervical cancer. One hundred and twenty-one operations were laparoscopic hysterectomies and 21 were laparoscopic radical hysterectomies. The overall conversion rate was 0.7%. The median length of the operation, the length of stay in hospital, the intraoperative complications, the lymph node yield, and the postoperative complication rates were comparable with previously published data from other institutions. At a median follow-up time of 29 months, the recurrence rates were 4.1% and 14.2% for laparoscopic hysterectomy and laparoscopic radical hysterectomy, respectively. Conclusion: Laparoscopic surgery for gynecological cancers at our institution is safe, with morbidity statistics comparable with those of other centers

hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts.

BackgroundWith their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts.MethodsWe derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs. The expression of DC-related genes and surface molecules was evaluated, as well as their DCL capacity to stimulate allogeneic T cells and induce regulatory T (Treg) cells in vitro. Using an immune system humanized mouse model, we investigated whether the adoptive transfer of CP DCLs can induce long-term immune tolerance of parental hESC-derived smooth muscle and cardiomyocyte allografts.FindingsCP DCLs can maintain immune suppressive properties after robust inflammatory stimulation and induce Treg cells. While CP DCLs survive transiently in vivo, they induce long-term immune tolerance of parental hESC-derived allografts.InterpretationThis strategy does not cause systemic immune suppression but induces immune tolerance specific for DCL-specific HLAs, and thus it presents a safe and effective approach to induce immune tolerance of allografts derived from any clinically approved hESC line.FundingNSFC, leading talents of Guangdong Province Program (No. 00201516), Key R&D Program of Guangdong Province (2019B020235003), Science and Technology Innovation Committee of Shenzhen Municipality (JCYJ20180504170301309), National High-tech R&D Program (863 Program No. 2015AA020310), Shenzhen "Sanming" Project of Medicine (SZSM201602102), Development and Reform Commission of Shenzhen Municipality (S2016004730009), CIRM (DISC2-10559)

Risk factors for recurrence of gestational diabetes mellitus in southern Chinese awomen: a retrospective study

Objectives: Predictors of gestational diabetes mellitus (GDM) recurrence (GDMR) was determined in southern Chinese women. Material and methods: A total of 366 women with GDM who had two consecutive singleton deliveries at our hospital between January 2014 and October 2020 were enrolled in the current study. We retrospectively compared the clinical characteristics, fasting plasma glucose level (FPG-1), and oral glucose tolerance test-1h-1 and -2h-1 (OGTT 1hr-1: 1-h post-load glucose level during the first pregnancy and OGTT 2hr-1: 2-h post-load glucose level during the first pregnancy) for the first pregnancy between patients in the GDMR group (n = 166) and the non-GDMR group (n = 210). Results: The incidence of GDMR in the study population was 44.15%. During the first pregnancy, women in the GDMR group had significantly higher OGTT 1h-1, OGTT 2h-1, and FPG-1 + OGTT 1h + 2h-1 compared to the non-GDMR group. When the threshold of the FPG-1 + OGTT 1h + 2h-1 level in the first pregnancy was > 23.6 mmol/L, the specificity for predicting GDMR was 0.85, the sensitivity was 0.45, and the area under the receiver operating characteristic curve (ROC-AUC) was 0.70, indicating a 70% probability of predicting GDMR in the next pregnancy. Logistic regression analysis showed that patients with a combined abnormal FPG-1 + OGTT 1h + 2 h-1 level had a 10-fold increased risk for GDMR in subsequent pregnancies than patients with normal indicators (OR: 10.542, 95% CI: 3.097–35.881; p < 0.0001). Conclusions: The OGTT 1h-1 and OGTT 2h-1 are independent risk factors for GDMR in southern Chinese women. Women with an FPG-1 + OGTT 1h + 2h-1 threshold level > 23.6 mmol/L in the first pregnancy had a 10-fold greater probability of developing GDMR in the second pregnancy than women in the non-GDMR group

Machine learning assisted prediction of dielectric temperature spectrum of ferroelectrics

In material science and engineering, obtaining a spectrum from a measurement is often time-consuming and its accurate prediction using data mining can also be difficult. In this work, we propose a machine learning strategy based on a deep neural network model to accurately predict the dielectric temperature spectrum for a typical multi-component ferroelectric system, i.e., (Ba1−x−yCaxSry)(Ti1−u−v−wZruSnvHfw)O3. The deep neural network model uses physical features as inputs and directly outputs the full spectrum, in addition to yielding the octahedral factor, Matyonov–Batsanov electronegativity, ratio of valence electron to nuclear charge, and core electron distance (Schubert) as four key descriptors. Owing to the physically meaningful features, our model exhibits better performance and generalization ability in the broader composition space of BaTiO3-based solid solutions. And the prediction accuracy is superior to traditional machine learning models that predict dielectric permittivity values at each temperature. Furthermore, the transition temperature and the degree of dispersion of the ferroelectric phase transition are easily extracted from the predicted spectra to provide richer physical information. The prediction is also experimentally validated by typical samples of (Ba0.85Ca0.15)(Ti0.98–xZrxHf0.02)O3. This work provides insights for accelerating spectra predictions and extracting ferroelectric phase transition information.</p