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Gestational diabetes mellitus (GDM) is defined as the first onset of glucose intolerance in pregnancy without prior known diabetes. While it is commonly associated with metabolic risk factors such as obesity and hypertension, a small percentage of women with GDM have underlying autoimmune causes, with presence of islet-cell antibodies resulting in autoimmune-mediated destruction of the pancreas. We present a case of idiopathic postpartum pancreatitis precipitating fulminant diabetic ketoacidosis in a patient with otherwise well-controlled GDM during pregnancy, and subsequent findings of positive anti-glutamic acid decarboxylase antibody. This is the first presentation of autoimmune diabetes diagnosed postnatally in a woman who has no previous medical or family history.

Background: Artemisiae capillariae (Yinchen, YC) is a well-known herbal medicine used to treat drug-induced liver diseases, while the bioactive phytochemicals and pharmacological targets of YC remain unclear. Objective: The study aimed to probe the key active components in YC and determine the potential molecular mechanisms of YC protect against DILI Method: In this study, we first delved into the active chemicals and targets of YC, identified potential anti-AILI targets for YC, mapped the components-targets network, performed protein-protein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analyses of the action targets. This led to figure out the liver protective mechanism of YC against AILI. Analyzing the molecular docking of key targets, binding domain of ingredients and targets reveals the effective interaction, and the binding energy explains the efficiency and stability of the interactions. Results: Network analysis identified 53 components in YC; by systematic screening 13 compounds were selected, which were associated with 123 AILI-related genes. The core ingredients were quercetin, capillarisin and Skrofulein, and the identified crucial genes were AKT1, TNF, and IL6. The GO and KEGG pathway enrichment analysis results indicated that the anti-AILI targets of YC mainly take a part in the regulation of oxidative stress and immune, with related signaling pathways including PI3K/AKT and IL17. Furthermore, the binding pockets of YC bioactive ingredients and key targets were revealed, and the binding ability was proved by molecular docking analysis. Conclusion: This study has revealed the potential bioactive molecules and mechanism of YC in AILI and provided a possible strategy for the identification of active phytochemicals against drug-induced liver injury.

Objectives A vast amount of literature has been conducted for investigating the association of different lunar phases with human health; and it has mixed reviews for association and non-association of diseases with lunar phases. This study investigates the existence of any impact of moon phases on humans by exploring the difference in the rate of outpatient visits and type of diseases that prevail in either non-moon or moon phases. Methods We retrieved dates of non-moon and moon phases for eight years (1st January 2001–31st December 2008) from the timeanddate.com website for Taiwan. The study cohort consisted of 1 million people from Taiwan's National Health Insurance Research Database (NHIRD) followed over eight years (1st January 2001–31st December 2008). We used the two-tailed, paired-t-test to compare the significance of difference among outpatient visits for 1229 moon phase days and 1074 non-moon phase days by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes from NHIRD records. Results We found 58 diseases that showed statistical differences in number of outpatient visits in the non-moon and moon phases. Conclusions The results of our study identified diseases that have significant variations during different lunar phases (non-moon and moon phases) for outpatient visits in the hospital. In order to fully understand the reality of the pervasive myth of lunar effects on human health, behaviors and diseases, more in-depth research investigations are required for providing comprehensive evidence covering all the factors, such as biological, psychological and environmental aspects.

Redox active, insoluble pyrene tetraone based dendritic porous polymers were synthesized by using different catalyst loadings and work-up procedures.

Traditionally, the participation patterns in the humanities and STEM (science, technology, engineering, and mathematics) programs in higher education differ. This study aimed to tackle this issue using concurrent time series data sets in the expanding higher education system. Authors selected the higher education system in Taiwan as an example. The participation in the humanities and STEM programs, covering 71 periods from 1950-2020, were collected from the Ministry of Education in Taiwan. The authors applied CCF (cross-correlation function) and ARIMAX (multivariable autoregressive integrated moving average) models to select the fittest model to predict the future trend. The humanities was the input variable and STEM was the output variable in the model. The findings revealed that ARIMAX (1,2,1) works well for these target data sets. According to the findings, enrollment in STEM programs will decrease with the decline in humanities programs in the future. This finding may provide useful information for related policy makers.

To investigate preferences of pregnant women for the characteristics of prenatal testing, and to quantify their willingness-to-pay (WTP) for non-invasive prenatal testing (NIPT) as first-line screening for Down Syndrome.A cross-sectional discrete choice experiment survey including five testing attributes was administered to 192 pregnant women (≤14 weeks' gestation) who were aged ≥21 years in Singapore. We calculated marginal WTP for improvements in testing characteristics and NIPT.We identified two groups of women with distinct preferences for prenatal testing. Women aged ≥35 years, with at least a university education, and with intention to terminate pregnancy of an affected fetus were more likely to be in the group with higher WTP for improvements in test characteristics. While participants valued increased detection rate and lower screen positive rate associated with NIPT, they also valued no risk of test failure and ability to test for birth defects using standard testing. The participants, on average, were not willing to pay for NIPT over the standard testing as a first-line screening test.As a first-line screening, NIPT was not preferred over standard testing. The prenatal consultations should focus on each testing characteristic equally as our findings show diverse preferences for testing characteristics.

M. tuberculosis (Mtb) within the caseous core of necrotic granulomas and cavities is extremely drug tolerant and presents a significant hurdle to treatment success and relapse prevention. Many in vitro models of nonreplicating persistence have been developed to characterize the physiologic and metabolic adaptations of Mtb and identify compounds active against this treatment-recalcitrant population.

The application scopes of two different reductive perturbation methods to derive the Korteweg–de Vries (KdV) equation and coupled KdV (CKdV) equation in two-temperature-ion dusty plasma are given by using the particle-in-cell (PIC) numerical method in the present paper. It suggests that the reductive perturbation method (RPM) is valid if the amplitude of the CKdV solitary wave is small enough. However, for the KdV solitary wave, RPM is valid not only if the amplitude of the KdV solitary wave is small enough, but also if the nonlinear coefficient of the KdV equation is not tending to zero.

Supplementary Figures S1-S4; Supplementary Tables S1-S3.

Supplementary Materials, Figures 1-7, Table 1 from A Novel Sialyltransferase Inhibitor Suppresses FAK/Paxillin Signaling and Cancer Angiogenesis and Metastasis Pathways

Background Salicylic Acid (SA) is a pivotal phytohormone in plant innate immunity enhancement of triggered by various pathogens, such as Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). WRKY is a plant specific transcription factor (TF) family, which plays crucial roles in plant response to biotic stresses. So far, the evolutionary history, functions, and expression patterns under SA treatment and CLas infection of WRKY family are poorly understood in Citrus, despite the release of the genome of several Citrus species. A comprehensive genomic and expressional analysis is worth to conduct for this family. Results Here, a genome-wide identification of WRKY TFs was performed in two Citrus species: Citrus sinensis (HLB-sensitive) and Poncirus trifoliata (HLB-tolerant). In total, 52 CsWRKYs and 51 PtrWRKYs were identified, whose physical and chemical properties, chromosome locations, phylogenetic relationships and structural characteristics were comparatively analyzed. Especially, expression patterns of these WRKY genes before and after SA treatment and CLas infection were compared. Based on this result, seven pairs of orthologous WRKY genes showing opposite expression patterns in two Citrus species were screened out. Moreover, two pairs of orthologous WRKY genes with significant differences in the number or type of stress-responsive cis-elements in the promoter regions were discovered. Subcellular localization and transcriptional activation activity assays revealed that these two pairs of orthologous genes are classic WRKY TFs localize in the nucleus and could function as transcriptional activators. Conclusion In this study, we systematically analyzed the genomic characterization of WRKY family in two Citrus species, together with the analyses of expression patterns under SA signaling and CLas infection. Our study laid a foundation for further study on the function of WRKY TFs in HLB response and SA signaling of Citrus.

Most ergot alkaloid drugs are semi-synthetically derived from the natural product lysergic acid, a valuable precursor for the development of novel ergot alkaloid drugs. Clavine oxidase (CloA) is a putative cytochrome P450, identified in the ergot alkaloid biosynthesis pathway, and a key enzyme that catalyzes the formation of lysergic acid from the precursor alkaloid agroclavine in a two-step oxidation reaction. We demonstrated in this study that Saccharomyces cerevisiae can be used as a viable host for the functional expression of CloA from Claviceps purpurea and its orthologs. We also showed that CloA orthologs differ in their ability to oxidize the substrate agroclavine, with some orthologs only able to perform the first oxidation reaction to produce elymoclavine. Of particular note, we identified a region between the F-G helices of the enzyme that may be involved in directing oxidation of agroclavine by substrate recognition and uptake. Using this knowledge, engineered CloAs were shown to produce lysergic acid at levels exceeding that of wildtype CloA orthologs; a CloA variant, chimeric AT5 9Hypo CloA, increased production levels of lysergic acid to 15 times higher as compared to the wildtype enzyme, demonstrating future utility for the industrial production of ergot alkaloids using biosynthetic routes.

The study aimed to investigate whether serum sFlt-1 (soluble fms-like tyrosine kinase-1) at 11-13 weeks’ gestation in pregnancies that subsequently developed preeclampsia was different from those without preeclampsia and compare screening performance of the International Prediction of Pregnancy Complications (IPPIC) reported models, which include various combinations of maternal factors, systolic blood pressure, diastolic blood pressure, PlGF (placental growth factor) and sFlt-1 and the competing risk (CR) models, which include various combinations of maternal factors, mean arterial pressure (MAP) and PlGF for predicting any-onset, early-onset, and late-onset preeclampsia. This was a prospective multicenter study in 7877 singleton pregnancies. The differences of the predictive performance between the IPPIC and CR models were compared. There were 141 women (1.79%) who developed preeclampsia, including 13 cases (0.17%) of early-onset preeclampsia and 128 cases (1.62%) of late-onset preeclampsia. In pregnancies that developed preeclampsia compared to unaffected pregnancies, median serum sFlt-1 levels and its MoMs were not significantly different ( p >0.05). There was no significant association between gestational age at delivery and log 10 sFlt-1 and log 10 sFlt-1 MoM ( p >0.05). The areas under the curve of CR models were significantly higher than the IPPIC models for the prediction of any-onset and late-onset preeclampsia but not for early-onset preeclampsia. In conclusion, there are no significant differences in the maternal serum sFlt-1 levels at 11-13 weeks’ gestation between women who subsequently develop preeclampsia and those who do not. Moreover, the CR models for the prediction of any-onset and late-onset preeclampsia perform better than the IPPIC reported model.

As the third-generation supramolecular main structure, calixarenes, especially chiral calixarenes, have been applied to various fields. In this study, the bridging chiral de-tert-butylcalix[4]arene derivatives with an amide group attached to a chiral point was synthesized for the first time, which provided a new group for its structural derivation at the bridging chiral position. The racemic compound 2 was optically resolved by column chromatography on silica gel with the aid of the chiral auxiliary (1S)-(+)-10-camphorsulfonyl chloride, and finally a pair of optically pure bridging chiral de-tert-butylcalix[4]arene derivatives 4a and 4b were obtained. The results of experimental and calculated ECD showed that compounds 4a and 4b were a pair of enantiomers, and their absolute configurations were designated S and R, respectively. This study provides new idea for the derivatization of specific chiral groups based on bridging chiral calix[4]arenes and their chiral resolution.

A dual phase structure consisting of ferrite and martensite has been achieved in Ti-bearing steels microalloyed with Mo or Cu, respectively, which were treated under different austenitizing and hot deformation conditions to investigate the effects of second microalloying elements and thermomechanical processes on the microstructural evolution and mechanical properties. The results showed the largest microhardness values, 343 HV0.1 for Ti–Mo steel and 307 HV0.1 for Ti–Cu steel, in microalloyed steels austenitized at 1200 °C with 30% deformation strain. Furthermore, critical patent analysis revealed that higher tensile strength is achieved in a Ti–Mo steel having a larger Ti/Mo atomic ratio, but no such relationship between tensile strength and Ti/Cu atomic ratio applies to Ti–Cu steel. This finding can be ascribed to the different metallurgical effects of Mo and Cu in the Ti-bearing steels. For example, the addition of Mo in a Ti-bearing steel leads to tiny carbides due to the decrease in coarsening via the synergistic effect of Ti and Mo. On the other hand, the separate precipitation of TiC and Cu in the Ti-bearing steels is consistent with the results of patent analysis. That is, the tensile strength of these steels is not associated with the Ti/Cu atomic ratio.

Purpose To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. Materials and methods Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. Results From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. Conclusions Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

We report on the methodology of developing a hybrid model and utilizing it as a template to initiate running behavior in a legged robot. The hybrid model is comprised of a physics-based, rolling, spring-loaded, inverted pendulum (R-SLIP) model, and a data-driven model that compensates for unmodeled dynamics using Gaussian process (GP) regression. The hybrid R-SLIP-GP model retains the R-SLIP's intrinsic running dynamics, as well as improves the template's accuracy without intensive data training and iteration efforts. The proposed hybrid model was evaluated via simulation and in empirical robot running experiments. The results confirm that the added GP-based model greatly improved the model's accuracy, especially discrepancies resulting from the originally difficult-to-model complex leg-ground interactions. In addition, the R-SLIP-GP model was utilized as a complete motion template to design and control the robot's running motion. The experimental results demonstrate that the hybrid template can initiate more stable and power-efficient running motion in the robot than using the R-SLIP template.

Proteomic tools were used to identify the key proteins that might be associated with bronchial asthma(BA). Firstly, the serum samples from healthy adults and asthmatic patients were collected. Tandem Mass Tag~(TM)(TMT), which removes high-abundance structures and nonspecific proteins, was employed to identify the differentially expressed proteins between asthmatic patients and healthy adults. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out for the differentially expressed proteins. The core proteins in the asthma group were screened out by protein-protein interaction(PPI) analysis. Then the core proteins were verified by Western blot for 3 patients with bronchial asthma and 3 healthy adults. A total of 778 differentially expressed proteins were screened out, among which 32 proteins contained quantitative information, including 18 up-regulated proteins and 14 down-regulated proteins. The differentially expressed proteins were enriched in 28 KEGG signaling pathways. The PPI analysis showed that 10 proteins(GDN, 1433 Z, VWF, HEMO, CERU, A1 AT, TSP1, G3 P, IBP7, and KPYM) might be involved in the pathogenesis of bronchial asthma. Compared with those in healthy adults, the expression levels of SLC25 A4, SVEP1, and KRT25 in the sera of asthmatic patients were up-regulated(Plt;0.05). Therefore, it is hypothesized that a variety of immune signaling pathways and differentially expressed proteins play a role in the pathogenesis of BA, which provides potential target information for the treatment of BA.

Ferroptosis is one of the critical pathological events in spinal cord injury. Erythropoietin has been reported to improve the recovery of spinal cord injury. However, whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined. In this study, we established rat models of spinal cord injury by modified Allen's method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks. Both low and high doses of erythropoietin promoted recovery of hindlimb function, and the high dose of erythropoietin led to better outcome. High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin. The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1 (a ferroptosis suppressor), and the effects of erythropoietin were largely diminished by RSL3 (ferroptosis activator). In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4. This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury. Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.