PagMYB151 facilitates proline accumulation to enhance salt tolerance of poplar.

Poplar is one of the main urban and rural greening and shade tree species in the northern hemisphere, but its growth and development is always restricted by salt stress. R2R3-MYB transcription factor family is commonly involved in many biological processes during plant growth and stress endurance. In this study, PagMYB151 (Potri.014G035100) one of R2R3-MYB members related to salt stress and expressed in both nucleus and cell membrane was cloned from Populus alba × P. glandulosa to perfect the salt tolerance mechanism. Morphological and physiological indexes regulated by PagMYB151 were detected using the PagMYB151 overexpression (OX) and RNA interference (RNAi) transgenic poplar lines. Under salt stress conditions, compared with RNAi and the non-transgenic wild-type (WT) plants, the plant height, both aboveground and underground part fresh weight of OX was significantly increased. In addition, OX has a longer and finer root structure and a larger root surface area. The root activity of OX was also enhanced, which was significantly different from RNAi but not from WT under salt treatment. Under normal conditions, the stomatal aperture of OX was larger than WT, whereas this phenotype was not obvious after salt stress treatment. In terms of physiological indices, OX enhanced the accumulation of proline but reduced the toxicity of malondialdehyde to plants under salt stress. Combing with the transcriptome sequencing data, 6 transcription factors induced by salt stress and co-expressed with PagMYB151 were identified that may cooperate with PagMYB151 to function in salt stress responding process. This study provides a basis for further exploring the molecular mechanism of poplar PagMYB151 transcription factor under abiotic stress.

Transcription Factor ERF194 Modulates the Stress-Related Physiology to Enhance Drought Tolerance of Poplar.

Drought is one of the main environmental factors limiting plant growth and development. The AP2/ERF transcription factor (TF) ERF194 play key roles in poplar growth and drought-stress tolerance. However, the physiological mechanism remains to be explored. In this study, the ERF194-overexpression (OX), suppressed-expression (RNA interference, RNAi), and non-transgenic (WT) poplar clone 717 were used to study the physiology role of ERF194 transcription factor in poplar growth and drought tolerance. Morphological and physiological methods were used to systematically analyze the growth status, antioxidant enzyme activity, malondialdehyde (MDA), soluble sugars, starch, and non-structural carbohydrate (NSC) contents of poplar. Results showed that, compared with WT, OX plants had decrease in plant height, internode length, and leaf area and increased number of fine roots under drought stress. In addition, OX had higher water potential, activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), contents of chlorophyll, soluble sugar, starch, and NSC, implying that ERF194 positively regulates drought tolerance in poplar. The growth status of RNAi was similar to those of WT, but the relative water content and CAT activity of RNAi were lower than those of WT under drought treatment. Based on the transcriptome data, functional annotation and expression pattern analysis of differentially expressed genes were performed and further confirmed by RT-qPCR analysis. Gene ontology (GO) enrichment and gene expression pattern analysis indicated that overexpression of ERF194 upregulated the expression of oxidoreductases and metabolism-related genes such as POD and SOD. Detection of cis-acting elements in the promoters suggested that ERF194 may bind to these genes through MeJA-responsive elements, ABA-responsive elements, or elements involved in defense and stress responses. The above results show that ERF194 improved tolerance to drought stress in poplar by regulating its growth and physiological factors. This study provides a new idea for the role of ERF194 transcription factor in plant growth and drought-stress response.

Safety and immunogenicity of COVID-19 vaccination in patients with hepatocellular carcinoma (CHESS-NMCID 2101): A multicenter prospective study.

Data on safety and immunogenicity of coronavirus disease 2019 (COVID-19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole-virion COVID-19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP-CorV, and WIBP-CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9-23.2) AU/ml at 45 (IQR: 19-72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ-glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003-1.049], p = 0.049). In conclusion, this study found that inactivated COVID-19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID-19. Future validation studies are warranted.

Fabrication of methylene blue-loaded ovalbumin/polypyrrole nanoparticles for enhanced phototherapy-triggered antitumour immune activation.

BACKGROUND: Phototherapy-triggered immunogenic cell death (ICD) rarely elicits a robust antitumour immune response, partially due to low antigen exposure and inefficient antigen presentation. To address these issues, we developed novel methylene blue-loaded ovalbumin/polypyrrole nanoparticles (MB@OVA/PPY NPs) via oxidative polymerization and π-π stacking interactions. RESULTS: The as-prepared MB@OVA/PPY NPs with outstanding photothermal conversion efficiency (38%) and photodynamic properties were readily internalized into the cytoplasm and accumulated in the lysosomes and mitochondria. Upon 808 nm and 660 nm laser irradiation, the MB@OVA/PPY NPs not only ablated tumour cells by inducing local hyperthermia but also damaged residual tumour cells by generating a large amount of reactive oxygen species (ROS), finally triggering the release of many damage-associated molecular patterns (DAMPs). Moreover, the MB@OVA/PPY NPs synergized with DAMPs to promote the maturation and improve the antigen presentation ability of DCs in vitro and in vivo. CONCLUSIONS: This work reported a PPY NPs-based nanoplatform to encapsulate the therepeutic proteins and absorb the functional molecules for combination therapy of tumours. The results demonstrated that the prepared MB@OVA/PPY NPs could be used as effective nanotherapeutic agents to eliminate solid tumours and trigger a powerful antitumour immune response.

Deep Learning-Based Automatic CT Quantification of Coronavirus Disease 2019 Pneumonia: An International Collaborative Study.

OBJECTIVE: We aimed to develop and validate the automatic quantification of coronavirus disease 2019 (COVID-19) pneumonia on computed tomography (CT) images. METHODS: This retrospective study included 176 chest CT scans of 131 COVID-19 patients from 14 Korean and Chinese institutions from January 23 to March 15, 2020. Two experienced radiologists semiautomatically drew pneumonia masks on CT images to develop the 2D U-Net for segmenting pneumonia. External validation was performed using Japanese (n = 101), Italian (n = 99), Radiopaedia (n = 9), and Chinese data sets (n = 10). The primary measures for the system's performance were correlation coefficients for extent (%) and weight (g) of pneumonia in comparison with visual CT scores or human-derived segmentation. Multivariable logistic regression analyses were performed to evaluate the association of the extent and weight with symptoms in the Japanese data set and composite outcome (respiratory failure and death) in the Spanish data set (n = 115). RESULTS: In the internal test data set, the intraclass correlation coefficients between U-Net outputs and references for the extent and weight were 0.990 and 0.993. In the Japanese data set, the Pearson correlation coefficients between U-Net outputs and visual CT scores were 0.908 and 0.899. In the other external data sets, intraclass correlation coefficients were between 0.949-0.965 (extent) and between 0.978-0.993 (weight). Extent and weight in the top quartile were independently associated with symptoms (odds ratio, 5.523 and 10.561; P = 0.041 and 0.016) and the composite outcome (odds ratio, 9.365 and 7.085; P = 0.021 and P = 0.035). CONCLUSIONS: Automatically quantified CT extent and weight of COVID-19 pneumonia were well correlated with human-derived references and independently associated with symptoms and prognosis in multinational external data sets.

Mediating Role of Mental Resilience between Sleep Quality and Mindfulness Level of Pregnant Women Screened by Prenatal Diagnosis.

OBJECTIVE: To explore the status quo of psychological resilience, mindfulness level, the sleep quality of pregnant women by Prenatal Diagnosis Screening, and the mediating effect of psychological resilience on sleep quality and mindfulness. METHODS: A survey of 298 pregnant women was conducted using the psychological resilience scale, Pittsburgh sleep quality index, and the concise version of the five-factor mindfulness scale. RESULTS: The total score of psychological resilience of pregnant women was (68.96 ± 17.27), mindfulness was (77.25 ± 12.65), the median of total sleep quality was 6, and the detection rate of sleep disorders was 31.9%. The sleep quality of pregnant women was negatively correlated with mindfulness level and psychological resilience (p < 0.01), and mindfulness level was positively associated with psychological resilience (p < 0.01). Bootstrap analysis showed that psychological resilience played an 14.1% mediating role between mindfulness and sleep quality. CONCLUSION: The psychological resilience of pregnant women is low, sleep quality is poor, and mindfulness is mild to moderate. Psychological resilience plays an important role in mediating between mindfulness level and sleep quality that suggests nursing staff should pay attention to and improve the psychological resilience of pregnant women screened by prenatal diagnosis to improve the mindfulness level and sleep quality of pregnant women screened by prenatal diagnosis.

Safety and Immunogenicity of SARS-CoV-2 Vaccines in Patients With Chronic Liver Diseases (CHESS-NMCID 2101): A Multicenter Study.

BACKGROUND & AIMS: We aimed to assess the safety and immunogenicity of inactivated whole-virion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with chronic liver diseases (CLD) in this study. METHODS: This was a prospective, multi-center, open-label study. Participants aged over 18 years with confirmed CLD and healthy volunteers were enrolled. All participants received 2 doses of inactivated whole-virion SARS-CoV-2 vaccines. Adverse reactions were recorded within 14 days after any dose of SARS-CoV-2 vaccine, laboratory testing results were collected after the second dose, and serum samples of enrolled subjects were collected and tested for SARS-CoV-2 neutralizing antibodies at least 14 days after the second dose. RESULTS: A total of 581 participants (437 patients with CLD and 144 healthy volunteers) were enrolled from 15 sites in China. Most adverse reactions were mild and transient, and injection site pain (n = 36; 8.2%) was the most frequently reported adverse event. Three participants had grade 3 aminopherase elevation (defined as alanine aminopherase >5 upper limits of normal) after the second dose of inactivated whole-virion SARS-CoV-2 vaccination, and only 1 of them was judged as severe adverse event potentially related to SARS-CoV-2 vaccination. The positive rates of SARS-CoV-2 neutralizing antibodies were 76.8% in the noncirrhotic CLD group, 78.9% in the compensated cirrhotic group, 76.7% in the decompensated cirrhotic group (P = .894 among CLD subgroups), and 90.3% in healthy controls (P = .008 vs CLD group). CONCLUSION: Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with CLD. Patients with CLD had lower immunologic response to SARS-CoV-2 vaccines than healthy population. The immunogenicity is similarly low in noncirrhotic CLD, compensated cirrhosis, and decompensated cirrhosis.

Safety and immunogenicity of COVID-19 vaccination in patients with non-alcoholic fatty liver disease (CHESS2101): A multicenter study.

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.

Machine learning-based CT radiomics method for predicting hospital stay in patients with pneumonia associated with SARS-CoV-2 infection: a multicenter study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a global challenge since the December 2019. The hospital stay is one of the prognostic indicators, and its predicting model based on CT radiomics features is important for assessing the patients' clinical outcome. The study aimed to develop and test machine learning-based CT radiomics models for predicting hospital stay in patients with COVID-19 pneumonia. METHODS: This retrospective, multicenter study enrolled patients with laboratory-confirmed SARS-CoV-2 infection and their initial CT images from 5 designated hospitals in Ankang, Lishui, Lanzhou, Linxia, and Zhenjiang between January 23, 2020 and February 8, 2020. Patients were classified into short-term (≤10 days) and long-term hospital stay (>10 days). CT radiomics models based on logistic regression (LR) and random forest (RF) were developed on features from pneumonia lesions in first four centers. The predictive performance was evaluated in fifth center (test dataset) on lung lobe- and patients-level. RESULTS: A total of 52 patients were enrolled from designated hospitals. As of February 20, 21 patients remained in hospital or with non-findings in CT were excluded. Therefore, 31 patients with 72 lesion segments were included in analysis. The CT radiomics models based on 6 second-order features were effective in discriminating short- and long-term hospital stay in patients with COVID-19 pneumonia, with areas under the curves of 0.97 (95% CI, 0.83-1.0) and 0.92 (95% CI, 0.67-1.0) by LR and RF, respectively, in test. The LR and RF model showed a sensitivity and specificity of 1.0 and 0.89, 0.75 and 1.0 in test respectively. As of February 28, a prospective cohort of six discharged patients were all correctly recognized as long-term stay using RF and LR models. CONCLUSIONS: The machine learning-based CT radiomics features and models showed feasibility and accuracy for predicting hospital stay in patients with COVID-19 pneumonia.

One-pot synthesis of cerium and praseodymium co-doped carbon quantum dots as enhanced antioxidant for hydroxyl radical scavenging.

The antioxidant activity of ceria nanoparticles is tightly regulated by size distribution and heteroatom doping. Inspired by this rule, cerium and praseodymium codoped carbon quantum dots (Ce/Pr-CQDs) were synthesized through the one-pot hydrothermal carbonization method. Taking intrinsic advantage of CQDs, the resultant Ce/Pr-CQDs exhibited uniform and ultra-small morphology with an average size of 2.8 nm, which led to an increased proportion of Ce3+. In addition, the doping of Pr into Ce-CQDs improved the redox properties. As we expected, the Ce/Pr-CQDs possessed enhanced hydroxyl radical scavenging properties compared with the cerium-doped carbon quantum dots (Ce-CQDs). Furthermore, Ce/Pr-CQDs with favorable biocompatibility and negligible cytotoxicity are readily internalized into cytoplasm, decreasing the level of reactive oxygen species (ROS). Taken together, the resultant Ce/Pr-CQDs displayed great potential for applications relating to oxidative-stress-associated disease.

Psychometric evaluation of undergraduate student nurses' learning perceived needs in disaster nursing: Two cross-sectional studies.

BACKGROUND: Disaster nursing education is a necessity for nurses and students to improve their disaster relief competencies. Determining undergraduate student nurses' learning perceived needs for disaster nursing can help improve curricula construction. In China there is currently no valid instrument available for the evaluation of influencing factors. A disaster nursing course content system was developed using the Delphi method in 2011. However, this system was unformed and lacked psychometric evaluation. OBJECTIVES: To adapt the disaster nursing course content system into an instrument, to evaluate its psychometric properties, and to investigate undergraduate student nurses' learning perceived needs for disaster nursing. DESIGN, SETTINGS AND PARTICIPANTS: Two cross-sectional studies were conducted in public higher education institutions in China. In the first study, a total of 1714 undergraduate student nurses were recruited in May to October 2016; in the second study, 68 were recruited in May 2019. METHODS: The instrument was adapted through literature review, face validity and pilot testing in preliminary studies. The construct validity and reliability of the instrument were tested using exploratory factor analysis, parallel analysis, confirmatory factor analysis, internal consistency reliability and test-retest reliability. RESULTS: The exploratory factor analysis and parallel analysis extracted a three-factor solution comprising 19 items that accounted for 71.69% of the total variance, including discipline introduction, skills and knowledge in disaster relief, and disaster management. The fit indices indicated a good fit. The internal consistency and test-retest reliability was good, as indicated by a Cronbach's alpha of 0.89 and an intraclass correlation coefficient of 0.87. CONCLUSION: The Learning Needs for Disaster Nursing questionnaire exhibited good psychometric properties, thereby proving itself a valuable instrument for evaluating learning perceived needs in undergraduate student nurses.

Construction of catechol-grafted chitosan alginate/barium sulfate microcapsules for computed tomography real-time imaging and gastroretentive drug delivery.

Background: The gastroretentive drug delivery system is an effective administration route, which can improve the bioavailability of the drug and the therapeutic effect by prolonging the release time of the drug and controlling the release rate in the stomach. Methods: Inspired by the excellent adhesion properties of mussel protein, we prepared novel catechol-grafted chitosan alginate/barium sulfate microcapsules (Cat-CA/BS MCs) with mucoadhesive properties and computed tomography (CT) imaging function for gastric drug delivery. First, barium sulfate nanoclusters used as CT contrast agent were synthesized in situ in the Cat-CA/BS MCs through a one-step electronic spinning method. Next, catechol-grafted chitosan as the mucoadhesive moiety was coated on the surface of Cat-CA/BS MCs by polyelectrolyte molecule self-assembly. Results: The prepared Cat-CA/BS MCs could effectively retained in the stomach for 48 hours and successively released ranitidine hydrochloride, which could be used for the treatment of gastric ulcer. Cat-CA/BS MCs exhibited superior CT contrast imaging properties for real-time tracking in vivo after oral administration. Conclusion: These findings demonstrate that Cat-CA/BS MCs serving as multifunctional oral drug carriers possess huge potential in gastroretentive drug delivery and non-invasive visualization.

Facile synthesis of cerium-doped carbon quantum dots as a highly efficient antioxidant for free radical scavenging.

Excessive reactive oxygen species (ROS) can lead to irreversible damage to the human body in vivo, therefore it is highly desirable to exploit an efficient antioxidant. Recently, cerium oxide nanoparticles have attracted extensive attention in the field of biomedicine due to their excellent antioxidant properties. In this study, cerium-doped carbon quantum dots (Ce-doped CQDs) with hydroxyl radical scavenging capacity were synthesized for first time by one-step hydrothermal carbonization method. The resultant Ce-doped CQDs with the average particle size of 2.5 nm possessed the properties of good water solubility, colloid stability, and strong fluorescence, which are similar to traditional CQDs. Meanwhile, the Ce-doped CQDs had good biocompatibility and negligible cytotoxicity. Taking advantage of inherent ultra-small size, the Ce-doped CQDs exhibited a high Ce3+/Ce4+ ratio at the surface of particles. The radical scavenging capability of the Ce-doped CQDs was proved by a simple photometric system in vitro, which provided direct evidence for its antioxidant potency. Furthermore, the Ce-doped CQDs had a high ability to protect cells from hydrogen peroxide-induced damage by scavenging hydroxyl radicals. These results suggest that Ce-doped CQDs as a new ROS scavenger may provide potential prospects for the treatment of oxidative stress-related diseases.

miR­498 inhibits the growth and metastasis of liver cancer by targeting ZEB2.

MicroRNAs (miRNAs) play critical roles in the growth, metastasis and therapeutic resistance of liver cancer. Accumulating evidence suggests that miR­498 is aberrantly expressed in several human malignancies. However, the role and underlying mechanism of miR­498 in liver cancer remain unclear. In the present study, we investigated the potential roles and clinical value of miR­498 in liver cancer. We found that the miR­498 expression level was significantly lower in liver cancer patient tissues than that in healthy control tissues. The expression of miR­498 was also decreased in liver cancer cell lines compared to that noted in a normal human normal liver cell line. miR­498 overexpression markedly inhibited liver cancer cell proliferation, migration and invasion. miR­498 overexpression induced cell cycle arrest and apoptosis while it suppressed epithelial­mesenchymal transition (EMT) in liver cancer cells. Bioinformatic analysis and luciferase reporter assay further identified zinc finger E­box binding homeobox 2 (ZEB2) as a novel target of miR­498. Furthermore, ZEB2 knockdown recapitulated the inhibitory effects of miR­498 overexpression in liver cancer cells. ZEB2 overexpression rescued the inhibition of liver cancer cell proliferation, migration, and invasion by miR­498, indicating that ZEB2 acts as a downstream effector of miR­498 in liver cancer cells. Thus, we demonstrated that miR­498 suppresses the growth and metastasis of liver cancer cells, partly at least, by directly targeting ZEB2, suggesting that miR­498 may serve as a potential biomarker for the diagnosis and therapy of liver cancer.

Myeloperoxidase -463 G/A polymorphism is associated with lung cancer risk: A meta-analysis with 7420 cases and 9132 controls.

AIMS: Several studies evaluated the association between myeloperoxidase (MPO) -463 G/A polymorphism and the risk of lung cancer. However, the results were not stable. MATERIALS AND METHODS: Online electronic databases (PubMed, EMBASE, and Wanfang database) were searched. The strength of association between the MPO -463 G/A polymorphism and lung cancer risk was assessed by calculating odds ratios (OR) with 95% confidence interval (CI). RESULTS: A total of 22 studies with 7420 cases and 9132 controls on the association between MPO -463 G/A polymorphism and lung cancer risk were included for this meta-analysis. MPO -463 G/A polymorphism was associated with a significantly decreased risk of lung cancer (OR = 0.91; 95% CI: 0.85-0.98; I 2 = 25%). In the race subgroup analysis, Asians with MPO -463 G/A polymorphism had decreased lung cancer risk (OR = 0.81; 95% CI: 0.70-0.93; I 2 = 0%). However, Caucasians did not show significant result (OR = 0.93; 95% CI: 0.86-1.02; I 2 = 36%). In the subgroup analysis according to source of control, both population-based studies and hospital-based studies were marginally significantly associated with decreased risk of lung cancer (OR = 0.90; 95% CI: 0.82-1.00; I 2 = 41% and OR = 0.91; 95% CI: 0.82-1.01; I 2 = 0%). CONCLUSION: The present meta-analysis suggested that the MPO -463 G/A polymorphism carriers had a protective role in lung cancer.

In situ fabrication of radiopaque microcapsules for oral delivery and real-time gastrointestinal tracking of Bifidobacterium.

INTRODUCTION: Although oral administration of Bifidobacterium is a promising approach for diseases, lack of resistance to harsh conditions and real-time tracking in gastrointestinal system in vivo are still major challenges in basic research and clinical applications. MATERIALS AND METHODS: In this study, we fabricated a chitosan-coated alginate microcapsule loaded with in situ synthesized barium sulfate (CA/BaSO4 microcapsule) for oral Bifidobacterium delivery and real-time X-ray computed tomography (CT) imaging. CA/BaSO4 microcapsules containing the Bifidobacterium were prepared in situ by one-step electrostatic spraying method, and then coated with chitosan. RESULTS: The results indicated that CA/BaSO4 microcapsules with an average diameter of approximately 200 µm possessed favorable mechanical stability and X-ray attenuation capacity. Encapsulation of Bifidobacteria in the CA/BaSO4 microcapsules exhibited superior resistance to cryopreservation and gastric acid environment in vitro. After oral administration in mice, these CA/BaSO4 microcapsules could be real-time visualized by CT imaging and readily reached the intestine to release Bifidobacteria. CONCLUSION: The radiopaque CA/BaSO4 microcapsules provide a novel platform for efficient protection, non-invasive real-time monitoring and intestinal-targeted Bifidobacterium delivery.

Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation.

Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.