Expression and self-assembly of virus-like particles from porcine parvovirus and its application in antibody detection.

Porcine parvovirus (PPV) is a major causative agent in reproductive pig disease. The swine industry faces a significant economic and epizootic threat; thus, finding a reliable, quick, and practical way to detect it is essential. In this investigation, recombinant PPV VP2 protein was expressed in the Escherichia coli ( E. coli) expression systems. As shown by electron microscopy (TEM), Western blot, and hemagglutination (HA) assays, the recombinant VP2 protein was successfully assembled into virus-like particles (VLPs) after being expressed and purified. These VLPs had a structure that was similar to that of real PPV viruses and also exhibited HA activity. These VLPs induced high levels of PPV-specific antibody titers in mice after immunization, indicating that the VLPs may be beneficial as potential candidate antigens. VLPs were used as the coating antigens for the VLP ELISA, and the PPV VLPs-based ELISA displayed a high sensitivity (99%), specificity (93.0%) and agreement rate (98.3%) compared to HI assay, and the agreement rate of this ELISA was 97.5% compared to a commercial ELISA kit. Within a plate, the coefficient of variation (CV) was 10%, and between ELISA plates, the CV was 15%. According to a cross-reactivity assay, the technique was PPV-specific in contrast to other viral illness sera. The PPV VLP indirect-ELISA test for PPV detection in pigs with an inactivated vaccine showed that the PPV-positive rate varied among different sample sources from 88.2 to 89.6%. Our results indicate that this ELISA technique was quick, accurate, and repeatable and may be used for extensive serological research on PPV antibodies in pigs.

[Analysis of incidence and associated factors of preterm birth based on pre-pregnancy body mass index stratification].

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.

[Association between coagulation function indicators and placental abruption among preeclampsia-eclampsia pregnant women].

Objective: To explore the association between coagulation function indicators and placental abruption (PA) in different trimesters of pregnancy among preeclampsia-eclampsia pregnant women. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study and were diagnosed with preeclampsia, eclampsia and chronic hypertension with superimposed preeclampsia in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. The baseline and follow-up information were collected by questionnaire survey, and the coagulation function indicators in the first and third trimesters were obtained through medical records. The Cox proportional hazards model was used to analyze the association between the coagulation function indicators and PA. A restrictive cubic spline curve was used to draw the dose-response curve between the relevant coagulation function indicators and PA. Results: A total of 1 340 participants were included in this study. The age was (32.50±4.24) and the incidence of PA was 4.4% (59/1 340). After adjusting for relevant factors, Cox proportional hazards model showed that compared with the high-level classification of fibrinogen (FIB), participants within the middle-(HR=3.28, 95%CI: 1.27-8.48) and low-level (HR=3.84, 95%CI: 1.40-10.53) classification during the first trimester and within the low-level classification (HR=4.18, 95%CI: 1.68-10.39) during the third trimester were more likely to experience PA. Compared with the middle-level classification of pro-thrombin time (PT), the risk of PA in the participants within the low-level classification (HR=2.67, 95%CI: 1.48-4.82) was significantly higher in the third trimester. The restrictive cubic spline analysis showed a linear negative association between FIB and PA in the first and third trimesters, while PT and PA showed an approximately L-shaped association. Conclusion: Among pregnant women diagnosed with preeclampsia-eclampsia, the middle-and low-level classification of FIB in the first and third trimesters and the low-level classification of PT in the third trimester could increase the risk of PA.

[Progress in researches on cardiovascular health behaviors and factors in perinatal women].

The cardiovascular health index (CVH) is a composite index consisting of 7 CVH metrics (CVHM) to evaluate the cardiovascular health status in the population. CVH has been proven to be closely related to a variety of health outcomes and widely used in the prevention of many diseases and the evaluation of intervention effectiveness. This review summarizes the recent distribution of CVH and CVHM in pregnant women and the relationship between CVH and CVHM with adverse health outcomes, which aims to explore the application of CVH and CVHM in preventing pregnancy-related diseases and improving the long-term health level of perinatal women and their offspring.

Digitalization of hydraulic rotary drilling process for continuously mechanical profiling of siliciclastic sedimentary rocks.

Hydraulic rotary drilling can offer the essential information and core samplesa for the researches on solid earth. Recording the factual field drilling data and analyzing the hydraulic rotary coring process are challenging yet promising to utilize the massive drilling information in geophysics and geology. This paper adopts the drilling process monitoring (DPM) technique and records the four parameters of displacement, thrust pressure, upward pressure, and rotation speed in real-time series for profiling the siliciclastic sedimentary rocks along 108 m deep drillhole. The digitalization results with 107 linear zones represent the spatial distribution of drilled geomaterials including superficial deposits (fill, loess, gravelly soil), mudstone, silty mudstone, gritstone, and fine sandstone. The constant drilling speeds varying from 0.018 to 1.905 m/min present the in-situ coring resistance of drilled geomaterials. Furthermore, the constant drilling speeds can identify the strength quality of soils to hard rocks. The thickness distributions of the six basic strength quality grades are presented for all the sedimentary rocks and each individual type of the seven soil and rocks. The in-situ strength profile determined in this paper can be used to assess and evaluate the in-situ mechanical behavior of geomaterial along the drillhole and can provide a new mechanical-based assessment for determining the spatial distribution of geological strata and structures in subsurface. They are important since the same stratum at different depths can have different mechanical behavior. The results provide a novel quantitative measurement for continuously in-situ mechanical profiling by digital drilling data. The findings of the paper can offer a new and effective method for refinement and upgrading of in-situ ground investigation, and can provide researchers and engineers with a novel tool and valuable reference to digitize and utilize factual data of current drilling projects.

[Variations in fecal microbiota of first episode schizophrenia associated with clinical assessment and serum metabolomics].

OBJECTIVE: To explore the role of the microbiota in drug naïve first-onset schizophrenia patients and to seek evidence from multidimensional longitudinal analyses of the intestinal microbiome and clinical phenotype with antipsychotic drugs (APDs) therapy. METHODS: In this study, 28 drug naïve first onset schizophrenia patients and age-, gender- and education-matched 29 healthy controls were included, and the patients were treated with APDs. We collected fecal and serum samples at baseline and after 6 weeks of treatment to identify the different microbiota strains and analyse their correlation with clinical symptoms and serum metabolites. The 16S rRNA genes of the gut microbiota were sequenced, and the diversity and relative abundance at the phylum and genus levels were analyzsed in detail. The PANSS score, BMI changed value, and serum metabolome were included in the data analyses. RESULTS: A multiomics study found a potential connection among the clinical phenotype, microbiota and metabolome. The species diversity analyses revealed that the alpha diversity index (chao1, ACE, and goods_coverage) in the schizophrenia APDs group was significantly lower than that in the control group, and the schizophrenia group had clear demarcation from the control group. The microbiota composition analysis results showed that the relative abundance of the genera of Bacteroides, Streptococcus, Romboutsia, and Eubacterium ruminantium group significantly changed after APDs treatment in the schizophrenia patients. These strains could reflect the APDs treatment effect. More genera had differences between the patient and control groups. The LEfSe analysis showed that Prevotella_9 and Bacteroides were enriched in schizophrenia, while Blautia, Dialister, and Roseburia were enriched in the control group. The correlation analysis between microbiota and clinical symptoms showed that Bifidobacterium in schizophrenia was positively correlated with the PANSS reduction rate of the general psychopathology scale. The BMI changed value was positively correlated with the alteration of Clostridium_sensu_stricto_1 during treatment and the baseline abundance of Bacteroides. Moreover, metabolomic data analysis revealed a significant correlation between specific genera and metabolites, such as L-methionine, L-proline, homovanillic acid, N-acetylserotonin, and vitamin B6. CONCLUSION: Our study found some microbiota features in schizophrenia patients and healthy controls, and several strains were correlated with APDs effects. Furthermore, the multiomics analysis implies the intermediate role of microbiota between antipsychotic effects and serum metabolites and provides new evidence to interpret the difference from multiple levels in the pathogenesis and pharmacological mechanism of schizophrenia.

MicroRNA-29a-3p regulates chemosensitivity in hypopharyngeal carcinoma via targeting Cdc42.

INTRODUCTION: Hypopharyngeal carcinoma is one kind of high malignant tumour followed by poor prognosis in head and neck carcinomas. This study aimed to detect miR-29a-3p and Cdc42 in patients with hypopharyngeal carcinoma. MATERIALS AND METHODS: The expression of miR-29a-3p and Cdc42 mRNA were detected, and the correlation between miR-29a-3p/Cdc42 and clinical stages was investigated. RESULTS: The relative expression of miR-29a-3p in stage II, III and IV hypopharyngeal carcinoma tissues was significantly lower than that of stage I (P< 0.05). The relative expression of Cdc42 mRNA in stage I, III and IV tissues was significantly higher than that of stage I (P< 0.05). The expression of miR-29a-3p in hypopharyngeal carcinoma with lymph node metastasis was significantly lower than that without lymph node metastasis (P = 0.045). CONCLUSION: MiR-29a-3p and Cdc42 mRNA could be potential diagnostic biomarkers of hypopharyngeal carcinoma.

Muscle-derived stem cells in silk fibroin hydrogels promotes muscle regeneration and angiogenesis in sheep models: an experimental study.

OBJECTIVE: Silk fibroin (SF) hydrogels are of high interest in tissue engineering. However, angiogenesis is one of the major challenges in tissue regeneration and repair. In this study, we present a simple and effective method to develop a 1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol sodium salt (DMPG)-SF hydrogel. The SF hydrogels had no immunogenicity and approached natural tissues. MATERIALS AND METHODS: The SF scaffolds were first prepared from Bombyx mori silkworms and DMPG. The SF scaffold was seeded with muscle-derived stem cells derived from sheep embryo and implanted in the tibialis anterior muscle of mature sheep. Gelation time, H&E staining, and histochemistry were conducted and observed. The suitability of the hydrogels for 3D cell culture was assessed by living cell stain CM-Dil. RESULTS: The results showed that the SF hydrogels resembled the mechanical properties of natural soft tissues better. The results of H&E staining and histochemistry revealed that the degradation rate showed an S-type change, and muscle regeneration and angiogenesis were clearly visible. Adverse effects were not observed in the sheep models. CONCLUSIONS: DMPG-induced SF hydrogels can be successfully used for in situ cell encapsulation. It provides promising opportunities in biomedical applications, such as in tissue engineering and regeneration.

[Induction of peripheral blood mononuclear cells to hepatocyte-like cells and preliminary study of cell response to injury under the effect of acetaminophen].

Objective: To establish a method for the induction of peripheral blood mononuclear cells to hepatocyte-like cells, and preliminarily investigate cell response to injury under the effect of acetaminophen (APAP). Methods: The surface marker CD45 of peripheral blood mononuclear cells wase detected cells by using flow cytometry and immunofluorescence methods. The cellular morphology of induced hepatocyte-like cells was observed under an inverted microscope. Real-time fluorescent quantitative PCR (RT-PCR) was used to detect the expression level of hepatocyte-specific genes, such as cytochrome (CY) P1A2, CYP3A4, CYP2C9, albumin (ALB), alpha-fetoprotein (AFP), and hepatocyte nuclear factor (HNF)4α mRNA. Immunofluorescence method was used to detect intracellular hepatocyte markers AFP, HNF4α, and ALB expression at the protein level. Biochemical analyzer was used to detect hepatocyte-specific secretory functions of AFP, ALB, and urea. Luciferase chemiluminescence method was used to detect the activity of key drug metabolizing enzyme CYP3A4. Colorimetric assay was used to detect the effect of the drug acetaminophen on hepatocyte-like cells, and alanine aminotransferase (ALT) was used as an indicator of liver cell injury. The statistical differences between the data were compared with t-test and rank-sum test. Results: The positive expression rate of CD45 cell surface markers isolated from peripheral blood mononuclear cells was about 98%, and hepatocyte-like cell morphology changes appeared on 15th day of induction. Compared with isolated mononuclear cells, CYP1A2, CYP3A4, CYP2C9, ALB, AFP and HNF4α mRNA was markedly elevated. The expression level of AFP, ALB and HNF4α protein were equally increased, and the secretory function of AFP, ALB and urea were enhanced. Compared with primary hepatocytes, CYP1A2, CYP2C9, AFP, HNF4α mRNA, and CYP3A4 mRNA did not decrease. The expression levels of AFP, ALB, and HNF4α proteins in the cells did not decrease, and the secretory function of AFP, ALB, and urea did not decrease. In addition, the CYP3A4 enzyme activity produced by hepatocyte-like cells was similar to that of primary hepatocytes. Compared with hepatocyte-like cells incubated without APAP, hepatocyte-like cells incubated with APAP had higher ALT level. Under the effect of APAP, the ALT level of hepatocyte-like cells was higher than isolated mononuclear cells. Conclusion: Peripheral blood mononuclear cells can be induced into hepatocyte-like cells with partial characteristics of hepatocytes, including the activity of CYP3A4, a key enzyme of hepatocyte drug metabolism. Additionally, preliminarily ALT secretory features reflect the hepatocytes injury under the effect of acetaminophen.

The human hepatocyte TXG-MAPr: gene co-expression network modules to support mechanism-based risk assessment.

Mechanism-based risk assessment is urged to advance and fully permeate into current safety assessment practices, possibly at early phases of drug safety testing. Toxicogenomics is a promising source of mechanisms-revealing data, but interpretative analysis tools specific for the testing systems (e.g. hepatocytes) are lacking. In this study, we present the TXG-MAPr webtool (available at https://txg-mapr.eu/WGCNA_PHH/TGGATEs_PHH/ ), an R-Shiny-based implementation of weighted gene co-expression network analysis (WGCNA) obtained from the Primary Human Hepatocytes (PHH) TG-GATEs dataset. The 398 gene co-expression networks (modules) were annotated with functional information (pathway enrichment, transcription factor) to reveal their mechanistic interpretation. Several well-known stress response pathways were captured in the modules, were perturbed by specific stressors and showed preservation in rat systems (rat primary hepatocytes and rat in vivo liver), with the exception of DNA damage and oxidative stress responses. A subset of 87 well-annotated and preserved modules was used to evaluate mechanisms of toxicity of endoplasmic reticulum (ER) stress and oxidative stress inducers, including cyclosporine A, tunicamycin and acetaminophen. In addition, module responses can be calculated from external datasets obtained with different hepatocyte cells and platforms, including targeted RNA-seq data, therefore, imputing biological responses from a limited gene set. As another application, donors' sensitivity towards tunicamycin was investigated with the TXG-MAPr, identifying higher basal level of intrinsic immune response in donors with pre-existing liver pathology. In conclusion, we demonstrated that gene co-expression analysis coupled to an interactive visualization environment, the TXG-MAPr, is a promising approach to achieve mechanistic relevant, cross-species and cross-platform evaluation of toxicogenomic data.

Entropic stochastic resonance induced by a transverse driving force.

The phenomenon of entropic stochastic resonance (ESR) is investigated with the presence of a time-periodic force in the transverse direction. Simulation results manifest that the ESR can survive even if there is no static bias force in any direction, just if a transverse driving field is applied. In the weak noise region, the transverse driving force leads to a giant-suppression of the escape rate from one well to another, i.e. the entropic trapping. The increase in noise intensity will eliminate this suppression and induce the ESR phenomenon. An alternative quantity, called the mean free flying time, is also proposed to characterize the ESR as well as the conventional spectral power amplification. The ESR can be modulated conveniently by the transverse periodic force, which implies an alternative method for controlling the dynamics of small-scale systems. This article is part of the theme issue 'Vibrational and stochastic resonance in driven nonlinear systems (part 2)'.

Specific binding of aspartic protease and enterocytes promotes Trichinella spiralis invasion of murine intestinal epithelium cells.

Trichinella spiralis is an important foodborne zoonotic parasite and it is necessary to develop vaccine to prevent T. spiralis infection in food animals. T. spiralis aspartic protease-2 (TsASP2) has been demonstrated to play a crucial role in larval invasion of intestinal epithelium cells (IECs). The purpose of this study was to assess the interaction between TsASP2 and IECs and to investigate the immune protection elicited by vaccination with rTsASP2. The results showed that the enzymatic activity of native aspartic protease was detected in crude proteins of all T. spiralis development stages other than NBL stage, the highest activity was observed in the IIL stage. The results of Western blot showed that TsASP2 protein was expressed at ML, IIL and AW but not NBL, and the TsASP2 expression level at IIL stage was significantly higher than those of other three worm stages (P < 0.05). The specific binding between rTsASP2 and IECs was observed by immunofluorescence test (IFT) and confocal microscopy, and the binding site was localized at the IEC membrane and this binding ability was inhibited by aspartic protease specific inhibitor pepstain A. The results of ELISA showed that the binding ability was protein dose-dependent. Vaccination with rTsASP2 triggered a mixed Th1/Th2 humoral and mucosal immune responses, as demonstrated by the elevation levels of Th1/Th2 cytokines (IFN-γ and IL-4) secreted by the spleen and mesenteric lymph nodes (MLNs) of immunized mice. The mice vaccinated with rTsASP2 exhibited a 54.17% reduction in enteral adult worms and a 54.58% reduction in muscle larvae after T. spiralis challenge. The results demonstrated that TsASP2 might be a potential molecular target for anti-Trichinella vaccines.

Short lingual frenum in infants, children and adolescents. Part 2: Lingual frenum release. Functional surgical approach.

AIM: The aim of this study was to review the craniofacial growth impairment and different malfunctions associated with short lingual frenum and to assess the validity of lingual frenum surgery based on minimally invasive laser release with a myofunctional approach. MATERIALS AND METHODS: Thirty patients, children and adolescents whose ages ranged from 8 years to 18 years, diagnosed with a short lingual frenum and concomitant orthodontic problems and/or presence of associated muscular or postural problems, were treated in this study. Pre-operative tongue assessment was performed following morphological and functional criteria, consisting of measurement of the free tongue, and of visual assessment of tongue protrusion out of the mouth and elevation to the incisive palatal papilla. Postural evaluation was assessed in frontal and lateral view. Laser surgery was completed with local anaesthesia, using Erbium YAG laser (2940 nm, LightWalker, AT-Fotona, Ljubljana, Slovenia) equipped with sapphire conical tip (600 micron), with energy ranging from 120 to 160 mJ, at 15 Hz frequency, and varying the adjustable pulse duration from 300 µs to 600 µs. RESULTS: Significant improvement was noted in 29 of 30 patients comparing preoperative scores to both three-week and two-month post-op scores. Postural improvement was found in 18 of 30 patients, indicating the multifactorial involvement of different causes for correct body posture. CONCLUSION: This study confirmed the validity of Erbium:YAG laser surgery as an effective technique in children and adolescents to release a short lingual frenum. The functional approach of the procedure performed with the Erbium:YAG laser, and the concomitant myofunctional therapy demonstrated to be simple and safe in children, and adolescents. Because of the multifactorial causes involved in correct body posture, an adequate osteopathic therapy is important to successfully complete the full body rehabilitation.

Specific binding of aspartic protease and enterocytes promotes Trichinella spiralis invasion of murine intestinal epithelium cells

@#Trichinella spiralis is an important foodborne zoonotic parasite and it is necessary to develop vaccine to prevent T. spiralis infection in food animals. T. spiralis aspartic protease-2 (TsASP2) has been demonstrated to play a crucial role in larval invasion of intestinal epithelium cells (IECs). The purpose of this study was to assess the interaction between TsASP2 and IECs and to investigate the immune protection elicited by vaccination with rTsASP2. The results showed that the enzymatic activity of native aspartic protease was detected in crude proteins of all T. spiralis development stages other than NBL stage, the highest activity was observed in the IIL stage. The results of Western blot showed that TsASP2 protein was expressed at ML, IIL and AW but not NBL, and the TsASP2 expression level at IIL stage was significantly higher than those of other three worm stages (P < 0.05). The specific binding between rTsASP2 and IECs was observed by immunofluorescence test (IFT) and confocal microscopy, and the binding site was localized at the IEC membrane and this binding ability was inhibited by aspartic protease specific inhibitor pepstain A. The results of ELISA showed that the binding ability was protein dose-dependent. Vaccination with rTsASP2 triggered a mixed Th1/Th2 humoral and mucosal immune responses, as demonstrated by the elevation levels of Th1/Th2 cytokines (IFN-γ and IL-4) secreted by the spleen and mesenteric lymph nodes (MLNs) of immunized mice. The mice vaccinated with rTsASP2 exhibited a 54.17% reduction in enteral adult worms and a 54.58% reduction in muscle larvae after T. spiralis challenge. The results demonstrated that TsASP2 might be a potential molecular target for anti-Trichinella vaccines.

LINC00887 regulates the proliferation of nasopharyngeal carcinoma via targeting miRNA-203b-3p to upregulate NUP205.

OBJECTIVE: The purpose of this study was to uncover the regulatory effect of LINC00887 on the progression of nasopharyngeal carcinoma (NPC) and the underlying mechanism. PATIENTS AND METHODS: Relative level of LINC00887 in NPC tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Thereafter, the regulatory effect of LINC00887 on proliferative ability in SUNE-1 and HK-1 cells was examined by cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Through Dual-Luciferase reporter gene assay and RNA-Binding Protein Immunoprecipitation (RIP) assay, the interaction in the regulatory loop LINC00887/miRNA-203b-3p/NUP205 was ascertained. At last, rescue experiments were conducted to clarify the involvement of the regulatory loop LINC00887/miRNA-203b-3p/NUP205 in the progression of NPC. RESULTS: Results showed that LINC00887 was upregulated in NPC tissues and cells, and its overexpression markedly stimulated the proliferative ability in NPC cells. In addition, a potential interaction in the regulatory loop LINC00887/miRNA-203b-3p/NUP205 was discovered, which was responsible for promoting the proliferative ability in NPC. CONCLUSIONS: LINC00887 promotes the proliferative ability in NPC via absorbing miRNA-203b-3p to upregulate NUP205.

Tuning electronic and optical properties of monolayer PdSe2 by introducing defects: first-principles calculations.

Based on the density functional theory, the electronic and optical properties of pristine monolayer PdSe2 with Pd or Se vacancy-defect are investigated. Our results show that the Se defect is energetically more favorable than that of Pd defect. The band gap reduces, and some new midgap states appear after the Pd or Se defects are introduced. In terms of the optical properties, the prominent anisotropic characters are remained. The obvious new peaks of the dielectric constant appear after introducing defects. The light absorption in the visible energy range expands based on the appearance of the midgap states induced by the Pd or Se defects. The changes of the refractive index and reflectivity are similar with those of the dielectric constants and the light absorption. The energy loss spectrum of the PdSe2 with Pd or Se defects is obviously different, which can be used to identify different defects in PdSe2. These findings provide effective strategies to tune electronic and optical properties of monolayer PdSe2 by introducing defects.

Correlation of SOCS3 gene polymorphism with childhood asthma.

OBJECTIVE: To explore the correlation of the suppressor of cytokine signaling 3 (SOCS3) gene polymorphism with childhood asthma. PATIENTS AND METHODS: A total of 204 asthma children (observation group) and 235 healthy children (control group) were enrolled. General clinical information of enrolled subjects was collected. Inflammatory factors and pulmonary function test indexes in each subject were examined. Moreover, the polymorphism of SOCS3 gene rs9914220 was detected with the TaqMan-MGB probe. RESULTS: Asthma children in the observation group exhibited higher levels of interleukin-4 (IL-4), IL-17, and IL-33 than those of the control group (p<0.05). The forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (%), peak expiratory flow (PEF), and FVC in the observation group were lower than those in the control group. However, the residual volume (RV), and RV/total lung capacity (TLC) ratio were higher in observation group than those in control group (p<0.05). Distribution frequency of the genotypes varied a lot between the two groups (p<0.05). However, we did not observe a significant difference in SOCS3 alleles between the two groups (p>0.05). According to the analysis of the genetic model, there were differences in dominant and cumulative models between the two groups (p<0.05), whereas the recessive model was not different between the two groups (p>0.05). CONCLUSIONS: Levels of inflammatory factors and pulmonary functions help to effectively monitor the progression of childhood asthma, thus increasing the clinical diagnosis rate. The polymorphism of the SOCS3 gene rs9914220 site is correlated with the onset of childhood asthma.

Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy.

Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by nonisoform-selective Aurora inhibitors, demonstrates the Aurora B/C-dominant cytokinesis failure and polyploidy phenotypes. Several Aurora inhibitors are in clinical trials for T/B-cell lymphoma, multiple myeloma, leukemia, lung, and breast cancers. Here, we describe an Aurora A-selective inhibitor, LY3295668, which potently inhibits Aurora autophosphorylation and its kinase activity in vitro and in vivo, persistently arrests cancer cells in mitosis, and induces more profound apoptosis than Aurora B or Aurora A/B dual inhibitors without Aurora B inhibition-associated cytokinesis failure and aneuploidy. LY3295668 inhibits the growth of a broad panel of cancer cell lines, including small-cell lung and breast cancer cells. It demonstrates significant efficacy in small-cell lung cancer xenograft and patient-derived tumor preclinical models as a single agent and in combination with standard-of-care agents. LY3295668, as a highly Aurora A-selective inhibitor, may represent a preferred approach to the current pan-Aurora inhibitors as a cancer therapeutic agent.