PREX2 contributes to radiation resistance by inhibiting radiotherapy-induced tumor immunogenicity via cGAS/STING/IFNs pathway in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. RESULTS: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. CONCLUSIONS: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.

Enhanced metal-free photocatalyst performance by synergistic Coupling of internal magnetic field and piezoelectric field.

Graphitic carbon nitride (g-C3N4) is a promising metal-free photocatalyst; however, its high carrier recombination rate and insufficient redox capacity limit its degradation effect on antibiotics. In order to overcome these shortcomings, the photocatalytic activity is improved by regulating the spin polarization state, constructing the internal electric field, and applying the external piezoelectric field. In this paper, the chlorine-doped and nitrogen-deficient porous carbon nitride composite carbon quantum dots (Nv-Cl/UPCN@CQD) has been synthesized successfully. The doping position of chlorine and spin polarization properties are verified by DFT calculation. The key intermediates *O2- and *OOH for the synthesis of reactive oxygen species were detected by in-situ infrared testing, which promotes the production of •O2- and H2O2. The degradation rate constant of Nv-Cl/UPCN@CQD for removal of tetracycline is 8.45 times higher than that of g-C3N4. The active oxygen production and degradation efficiency of piezoelectric photocatalysis under the synergistic effect of intense stirring and vis-light irradiation are much higher than those of photocatalysis and piezoelectric catalysis, and the conversion of H2O2 to •OH is promoted by piezoelectric field. This paper provides a reliable way to improve the performance of piezoelectric photocatalysts by adjusting their energy band, electronic structure and piezoelectric force.

Tendon-Inspired Anisotropic Hydrogels with Excellent Mechanical Properties for Strain Sensors.

Anisotropic conductive hydrogels mimicking the natural tissues with high mechanical properties and intelligent sensing have played an important role in the field of flexible electronic devices. Herein, tensile remodeling, drying, and subsequent ion cross-linking methods were used to construct anisotropic hydrogels, which were inspired by the orientation and functionality of tendons. Due to the anisotropic arrangement of the polymer network, the mechanical performance and electrical conductivity were greatly improved in specific directions. The tensile stress and elastic modulus of the hydrogel along the network orientation were 29.82 and 28.53 MPa, which were higher than those along the vertical orientation, 9.63 and 11.7 MPa, respectively. Moreover, the hydrogels exhibited structure-dependent anisotropic sensing. The gauge factors (GFs) parallel to the prestretching direction were greater than the GF along the vertical direction. Thus, the tendon-inspired conductive hydrogels with anisotropy could be used as flexible sensors for joint motion detection and voice recognition. The anisotropic hydrogel-based sensors are highly expected to promote the great development of emerging soft electronics and medical detection.

Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome.

Obstetric antiphospholipid syndrome (OAPS) is mediated by antiphospholipid antibodies (aPLs, and anti-ß2 glycoprotein I antibody is the main pathogenic antibody), and recurrent abortion, preeclampsia, foetal growth restriction and other placental diseases are the main clinical characteristics of placental pathological pregnancy. It is a disease that seriously threatens the health of pregnant women. Hydroxychloroquine (HCQ) was originally used as an anti-malaria drug and has now shown benefit in refractory OAPS where conventional treatment has failed, with the expectation of providing protective clinical benefits for both the mother and foetus. However, its efficacy and mechanism of action are still unclear. After clinical data were collected to determine the therapeutic effect, human trophoblast cells in early pregnancy were prepared and treated with aPL. After the addition of HCQ, the proliferation, invasion, migration and tubule formation of the trophoblast cells were observed so that the therapeutic mechanism of HCQ on trophoblast cells could be determined. By establishing an obstetric APS mouse model similar to the clinical situation, we were able to detect the therapeutic effect of HCQ on pathological pregnancy. The normal function of trophoblast cells is affected by aPL. Antibodies reduce the ability of trophoblast cells to invade and migrate and can impair tubule formation, which are closely related to placental insufficiency. HCQ can partially reverse these side effects. In the OAPS mouse model, we found that HCQ prevented foetal death and reduced the incidence of pathological pregnancy. Therefore, HCQ can improve pregnancy outcomes and reverse the aPL inhibition of trophoblast disease. In OAPS, the use of HCQ needs to be seriously considered.

H19 Promotes HCC Bone Metastasis Through Reducing Osteoprotegerin Expression in a Protein Phosphatase 1 Catalytic Subunit Alpha/p38 Mitogen-Activated Protein Kinase-Dependent Manner and Sponging microRNA 200b-3p.

BACKGROUND AND AIMS: Bone is the second most frequent site of metastasis for HCC, which leads to an extremely poor prognosis. HCC bone metastasis is typically osteolytic, involving the activation of osteoclasts. Long noncoding RNA H19 plays an important role in the pathogenesis of human cancers. Nonetheless, the mechanism underlying the participation of H19 in HCC bone metastasis remains unclear. APPROACH AND RESULTS: The current study established a mouse HCC bone metastasis model by using serial intracardiac injection and cell isolation to obtain cells with distinct bone metastasis ability. H19 was highly expressed in these cells and in clinical HCC bone metastasis specimens. Both osteoclastogenesis in vitro and HCC bone metastasis in vivo were promoted by H19 overexpression, whereas these processes were suppressed by H19 knockdown. H19 overexpression attenuated p38 phosphorylation and further down-regulated the expression of osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor. However, up-regulated OPG expression as well as suppressed osteoclastogenesis caused by H19 knockdown were recovered by p38 interference, indicating that p38 mitogen-activated protein kinase (MAPK)-OPG contributed to H19-promoted HCC bone metastasis. Furthermore, we demonstrated that H19 inhibited the expression of OPG by binding with protein phosphatase 1 catalytic subunit alpha (PPP1CA), which dephosphorylates p38. SB-203580-mediated inactivation of p38MAPK reversed the down-regulation of HCC bone metastasis caused by H19 knockdown in vivo. Additionally, H19 enhanced cell migration and invasion by up-regulating zinc finger E-box binding homeobox 1 through the sequestration of microRNA (miR) 200b-3p. CONCLUSIONS: H19 plays a critical role in HCC bone metastasis by reducing OPG expression, which is mediated by the PPP1CA-induced inactivation of the p38MAPK pathway; and H19 also functions as a sponge for miR-200b-3p.

Dual-Sensing, Stretchable, Fatigue-Resistant, Adhesive, and Conductive Hydrogels Used as Flexible Sensors for Human Motion Monitoring.

Hydrogel-based sensors serve as an ideal platform for developing personalized wearable electronics due to their high flexibility and conformability. However, the weak stretchability and inferior conductivity of hydrogels have severely restricted their large-scale application. Herein, a natural polymer-based conductive hydrogel integrated with favorable mechanical properties, good adhesive performance, and excellent fatigue resistance was fabricated via interpenetrating tannic acid (TA) into a chitosan (CS) cross-linked network in an acidic aqueous solution. The hydrogel was composed of a regular hierarchical porous structure, which was built by the hydrogen bonding between TA and CS. In addition, the hydrogels exhibited adjustable mechanical properties (maximum yield stress of 7000 Pa) and good stretchability (strain up to 320%). Benefiting from the abundant catechol groups of TA, the proposed hydrogels could repeatedly adhere to various material surfaces and could be easily peeled off without residue. Moreover, the hydrogel exhibited stable conductivity, high stretching sensitivity (gauge factor of 2.956), rapid response time (930 ms), and excellent durability (>300 cycles), which can be assembled as a strain sensor to attach to the human body for precise monitoring of human exercise behavior, distinguishing physiological signals, and recognizing speech. Furthermore, the prepared hydrogels also exhibited stable sensing performance to temperature. As a result, the hydrogels exhibited dual sensory performance for both temperature and strain deformation. It is anticipated that the incorporation of strain sensors and thermal sensors will provide theoretical guidance for developing multifunctional conductive hydrogels and pave a way for the versatile application of hydrogel-based flexible sensors in wearable devices and soft actuators.

The impact of cold spells on schizophrenia admissions and the synergistic effect with the air quality index.

OBJECTIVES: Under current global climate conditions, there are insufficient studies on the health influences of cold spells, especially on mental health. This study aimed to examine the effect of cold spells on schizophrenia admissions and to analyze the potential interaction effect with the air quality index (AQI). METHODS: Daily data on schizophrenia admissions and climatic variables in Hefei were collected from 2013 to 2019. Based on 20 definitions, the impacts of cold spells were quantified separately to find the most appropriate definition for the region, and meta-regression was used to explore the different effect sizes of the different days in a cold spell event. In addition, the potential interaction effect was tested by introducing a categorical variable, CSH, reflecting the cold spell and AQI level. RESULTS: The cold spell defined by temperature below the 6th centile while lasting for at least three days produced the optimum model fit performance. In general, the risk of schizophrenia admissions increased on cold spell days. The largest single-day effect occurred on the 12th day with RR = 1.081 (95% CI: 1.044, 1.118). In a single cold spell event, the effect of the 3rd and subsequent days of a cold spell (RR = 1.082, 95% CI: 1.036, 1.130) was higher than that on the 2nd day (RR = 1.054, 95% CI: 1.024, 1.085). Similarly, the effect of the 2nd day was also higher than that of the 1st day (RR = 1.027, 95% CI: 1.012, 1.042). We found a synergistic effect between cold spells and high AQI in the male group, and the relative excess risk due to interaction (RERI) was 0.018 (95% CI: 0.005-0.030). CONCLUSIONS: This study suggested that the impacts of cold spells should be considered based on the definition of the most appropriate for the region when formulating targeted measures of schizophrenia. The discovery of the synergistic effect was referred to help the selection of the timing of precautions for susceptible people.

Association between exposure to a mixture of metals, parabens, and phthalates and fractional exhaled nitric oxide: A population-based study in US adults.

The effects of environmental endocrine-disrupting chemicals (EDCs) (e.g., phthalates) on fractional exhaled nitric oxide (FeNO) in children have received much attention. However, few studies evaluated this relationship in adults, and the previous studies have considered only a unitary exposure or a set of similar exposures instead of mixed exposures, which contain complicated interactions. We aimed to evaluate simultaneously the relationship between three types of EDCs (six phthalate metabolites and two parabens in urine, two heavy metals in blood) and FeNO (as a continuous variable) in adults. Data of adults aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES, 2007-2012) were collected and analyzed. The generalized linear (GLM) regression model was used to explore the association of chemicals with FeNO. The combined effect of 10 chemicals on the overall association with FeNO was evaluated by the weighted quantile sum regression (WQS) model. In addition, The Bayesian kernel machine regression (BKMR) model was explored to investigate the interaction and joint effects of multiple chemicals with FeNO. Of the 3296 study participants ultimately included, among the GLMs, we found that mercury (Hg) (ß = 0.84, 95%CI:0.32-1.36, FDR = 0.01) and methyl paraben (MPB) (ß = 0.47, 95%CI:0.16-0.78, FDR = 0.015) were positively correlated with FeNO. In the WQS model, the combined effect of chemicals almost had a significantly positive association with FeNO and the top three contributors to the WQS index were Hg (40.2%), MECPP (22.1%), and MPB (19.3%). BKMR analysis showed that there may be interactions between MPB and Hg, Mono (carboxyoctyl) phthalate (MCOP) and Hg and the overall effect of the mixture showed a positive correlation with FeNO. In conclusion, our study strengthens the credibility of the view that EDCs can affect respiratory health. In the future, we should be particularly careful with products containing Hg, MECPP, MPB, and MEHP for the prevention of respiratory diseases.

Potential mechanism of oral baicalin treating psoriasis via suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ.

Psoriasis (PSO), an immune-mediated chronic inflammatory skin disease, has seriously affected the quality of patients' life. It is urgent to find effective medicines with lower costs and less side effects. Baicalin (HQG) is the main bioactive substance from Scutellaria baicalensis with effects of anti-inflammation and immunoregulation. Herein, we explored the effect of oral HQG treating PSO and its potential mechanism. Firstly, network pharmacology was used to predict that HQG may act on Estrogen, TNF-alpha (tumor necrosis factor, TNF), interleukin-17 (IL-17) signaling pathways and Th17 cell differentiation, especially the key targets including TNF, Proto-oncogene tyrosine-protein kinase Src, Peroxisome proliferator-activated receptor gamma and Matrix metalloproteinase-9. Imiquimod (IMQ)-induced mice were then used to study the effects of HQG treating PSO. HQG could significantly ameliorate the skin lesions, decrease the level of inflammatory factors and inhibit Th1/Th17 cell differentiation in IMQ-induced mice. Finally, transcriptome analysis of skin lesions integrated with the prediction of network pharmacology further demonstrated that the potential mechanism may be associated with suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ. In conclusion, this study suggested that HQG may be a promising agent for further studies in the search for therapeutic strategies to treat PSO in the future.

Depression and sleep disorders among AIDS orphans in an HIV/AIDS high-epidemic area in China.

BACKGROUND: The Liangshan Yi Autonomous Prefecture is home to the largest population of Yi ethnic minority within mainland China. Due to the high HIV/AIDS epidemic, many Yi children become AIDS orphans who lost one or both parents to AIDS-related causes. This study explored the prevalence and correlates of AIDS orphans' depressive symptom, sleep disorders and their comorbidity. METHODS: A cross-sectional survey was conducted to collect pertinent information from 467 AIDS orphans and 856 non-orphans of Yi ethnic minority. Depressive symptoms were screened by a two-item Patient Health Questionnaire (PHQ-2). The symptoms of insomnia were assessed by the Insomnia Severity Index (ISI), which was complemented by one item from the Pittsburgh Quality Sleep Index (PSQI) to measure the frequency of nightmare. RESULTS: The prevalence of depression (26.8% vs. 20.4%, P = 0.009) and comorbidity of depression, insomnia and nightmare (7.5% vs. 4.3%, P = 0.046) was significantly higher for AIDS orphans than for non-orphans. Risk factors such as ostracization and self-reported poor physical health had stronger effects on depressive symptoms and sleep disorders for AIDS orphans than for non-orphans. On the other hand, peer support, as an important protective factor, was significantly and negatively associated with depressive symptoms and sleep disorders for AIDS orphans. CONCLUSIONS: AIDS orphans of Yi ethnic minority reported higher levels of depressive symptoms and comorbidity of depression and sleep disorders than their non-orphan counterparts. These symptoms were exacerbated by ostracization and self-rated poor physical health but lowered by peer support.

Disparities of weather type and geographical location in the impacts of temperature variability on cancer mortality: A multicity case-crossover study in Jiangsu Province, China.

BACKGROUND: Considering the serious health burden caused by adverse weather events, increasing researches focused on the relationship between temperature variability (TV) and cause-specific mortality, but its association with cancer was not well explored. We aimed to investigate the impacts of TV on cancer mortality and examine the modifying effects of weather type and geographical location as well as other characteristics. MATERIALS AND METHODS: Daily city-specific data of cancer deaths, mean temperature (Tmean), maximum and minimum temperatures (Tmax and Tmin), relative humidity (RH), rainfall, and air pollutants were collected during 2016-2017 in 13 cities in Jiangsu Province, China. TV0-t was defined as the standard deviation of the daily Tmax and Tmin on the exposure 0-t days. A two-stage analysis was applied. First, a time-stratified case-crossover design was used to examine the odds ratio (OR) and attributable fraction of cancer mortality per 1 °C increase in TV by adjusting for potential confounders. Random effect meta-analysis was used to summarize the pooled ORs. Second, stratified analysis was performed for weather type, geographical location, demographics, and other city-level characteristics. The weather was defined as four types according to days during warm or cold season combined with high or low RH. RESULTS: A total of 303670 cases were included in our study. Meta-analysis showed that the ORs of cancer mortality per 1 °C increase in TV0-t significantly increased and peaked in TV0-2 (OR=1.0098, 95% CI: 1.0039-1.0157). The attributable fraction of TV0-2 on cancer mortality was 4.74%, accounting for 14395 deaths in the study period. Significant ORs of TV-related cancer mortality were found during the warm season combined with high RH and in the northern region of Jiangsu. Susceptible groups of TV-related cancer mortality were identified as female patients, patients aged 45-65 years, and those living in cities with lower per capita green area. CONCLUSIONS: TV can significantly increase the risk of cancer mortality, especially during warm and humid days and in the northern region of Jiangsu. Findings are of great significance to formulate urban planning, resource allocation, and health intervention to prolong the life of cancer patients.

Gli1 interacts with YAP1 to promote tumorigenesis in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the predominant esophageal cancer type in China. The aberrant activation of glioma-associated oncogene homolog1 (Gli1), a key factor in Hedgehog (Hh) signaling pathway, has been found in esophageal carcinoma. Moreover, Yes-associated protein 1 (YAP1), the major mediator of Hippo signaling pathway, has been linked to esophageal carcinoma progression. However, the precise roles and the underlying mechanism of both Gli1 and YAP1 in ESCC are unclear. Here, we found that Gli1 and YAP1 are overexpressed in ESCC and are associated with poor prognosis. In addition, we confirmed that knockdown of Gli1 or YAP1 suppresses ESCC cell growth, migration, and invasion in ESCC TE1 and EC109 cells. Significantly, Gli1 interacts with YAP1 in ESCC cells. Both Gli1 and YAP1 proteins are closely correlated with each other in human ESCC samples. Mechanistically, Gli1 upregulates YAP1 in a LATS1-independent manner. Conversely, YAP1 induces Gli1 by regulating phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Most importantly, we demonstrated that the interaction between Gli1 and YAP1 promotes ESCC tumor growth in vitro and in vivo. Our findings established a novel signaling mechanism by which the interaction between Gli1 and YAP1 promotes ESCC cell growth. This signaling regulation of the tumorigenesis provides a new therapeutic strategy for highly lethal ESCC.

Zn(II)-Based Coordination Polymer for Detection of Picric Acid in Aqueous Media and Treatment Effect against Deep Vein Thrombosis by Reducing P-ERK2 and p53 Expression.

The coordination polymers based on Zn(II) ions and the metal nodes which has chemical formula of {[Zn3(L)2(tib)2(H2O)2]·(DMF)2}n (1) was synthesized via using 1,3,5-tris(1-imidazolyl)benzene (tib) and 2,6-di(4-carboxylphenyl)pyridine-4-carboxylic acid (H3L) as ligands under solvothermal conditions. Given its strong luminescent emission at room temperature and the uncoordinated N-donor sites in the framework, the selective detection performance of 1 toward the nitroanalytes was studied, 1's sensitive fluorescence quenching reactions along with selectivity to the electron-deficient TNP over other analytes of nitro within the aqueous phase was studied via the method of fluorescence quenching titration. Furthermore, the treatment effect of the compound on the deep vein thrombosis (DVT) was evaluated. Firstly, the ELISA was carried out to determine IL-17A content. Then, the platelet function was determined via the western blot by measuring expression level of platelet activation signaling pathway protein p-ERK2 and p53.

TLR4/AP-1-Targeted Anti-Inflammatory Intervention Attenuates Insulin Sensitivity and Liver Steatosis.

Insulin resistance has been shown to be the common pathogenesis of many metabolic diseases. Metainflammation is one of the important characteristics of insulin resistance. Macrophage polarization mediates the production and development of metainflammation. Toll-like receptor 4 (TLR4) mediates macrophage activity and is probably the intersection of immunity and metabolism, but the detailed mechanism is probably not fully understood. Activated protein 1 (AP1) signaling pathway is very important in macrophage activation-mediated inflammation. However, it is unclear whether AP1 signaling pathway mediates metabolic inflammation in the liver. We aimed to investigate the effects of macrophage TLR4-AP1 signaling pathway on hepatocyte metabolic inflammation, insulin sensitivity, and lipid deposition, as well as to explore the potential of TLR4-AP1 as new intervention targets of insulin resistance and liver steatosis. TLR4 and AP1 were silenced in the RAW264.7 cells by lentiviral siRNA transfection. In vivo transduction of lentivirus was administered in mice fed with high-fat diet. Insulin sensitivity and inflammation were evaluated in the treated cells or animals. Our results indicated that TLR4/AP-1 siRNA transfection alleviated high-fat diet-induced systemic and hepatic inflammation, obesity, and insulin resistance in mice. Additionally, TLR4/AP-1 siRNA transfection mitigated palmitic acid- (PA-) induced inflammation in RAW264.7 cells and metabolic abnormalities in cocultured AML hepatocytes. Herein, we propose that TLR4-AP1 signaling pathway activation plays a crucial role in high fat- or PA-induced metabolic inflammation and insulin resistance in hepatocytes. Intervention of the TLR4 expression regulates macrophage polarization and metabolic inflammation and further alleviates insulin resistance and lipid deposition in hepatocytes.

The combination therapy of transarterial chemoembolisation and sorafenib is the preferred palliative treatment for advanced hepatocellular carcinoma patients: a meta-analysis.

BACKGROUND: To compare the efficacy of three types of palliative therapy for advanced hepatocellular carcinoma (HCC), including transarterial chemoembolisation (TACE) monotherapy, sorafenib alone and their combination. METHODS: The databases of PubMed, Embase and Cochrane Library were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) was used to investigate the binary variables, and the standardised mean difference (SMD) with its 95% CI was employed to evaluate the continuous variables. All statistical tests were performed by using Stata/SE, version 12.0. RESULTS: Thirty-one clinical studies, containing 5125 unique cases of patients with advanced HCC, were included. There were significant improvements in overall survival (OS) (pooled SMD = 2.54; 95% CI 1.74-3.34) and time to progression (TTP) (pooled SMD = 2.49; 95% CI 0.87-4.12) of the patients after receiving the combination therapy of TACE and sorafenib, compared to TACE monotherapy, and the OS in the combined treatment cohort was also longer than that in the sorafenib-alone cohort (pooled SMD = 2.92; 95% CI 1.72-4.13). The combination therapy group in comparison to the TACE group benefited a significantly increased overall response rate (ORR) (pooled OR = 2.61; 95% CI 1.43-4.77), 1-year (pooled OR = 2.96; 95% CI 1.71-5.14) and 2-year (pooled OR = 1.64; 95% CI 1.18-2.28) survival rates and reduced disease progression rate (DPR) (pooled OR = 0.47; 95% CI 0.33-0.68); in parallel, the ORR in the group was also significantly higher than that in the sorafenib-alone group (pooled OR = 3.62; 95% CI 1.28-10.22), although without a difference in the DPR (pooled OR = 0.28; 95% CI 0.05-1.48). In addition, we discovered that the 1-year (pooled OR = 1.39; 95% CI 0.84-2.29) and 2-year (pooled OR = 1.70; 95% CI 0.69-4.18) survival rates in the TACE monotherapy cohort were not significantly different to those in the sorafenib-alone cohort. CONCLUSION: The combination therapy is more effective than monotherapy in improving the prognostic outcomes of patients with advanced HCC. Therefore, we recommend it as the preferred treatment intervention for those patients.

[Influencing factors of depressive symptoms of rural middle school students in Zizhong County based on two-level Logistic regression model].

OBJECTIVE: To understand the prevalence of depressive symptoms of middle school students in rural areas of Zizhong County, and to analyze its main influencing factors. METHODS: In October 2015, two rural middle schools in Zizhong County, Sichuan Province, were selected to conduct a self-administered questionnaire survey(general demographic characteristics, the center for epidemiological studies depression scale(CES-D), self-esteem scale(SES) and connor-davidson resilience scale(CD-RICS)) on all the students(there were 2744 effective persons, including 1308 boys and 1436 girls, 554 middle school students and 2190 high school students), and then carried out a follow-up survey every semester. RESULTS: The prevalence of depressive symptoms was 30. 5%(in the baseline survey, it was 26. 7%, the third 35. 7% and the fifth 29. 8%), and the rate of female students was 30. 3%, higher than that of male students 22. 9%(χ~2=19. 72, P<0. 05). The main influencing factors of depressive symptoms of rural middle school students in Sichuan were gender(ß=0. 201, P=0. 001), be aware of whether teacher liked or not(ß=0. 228, P=0. 005), be aware of whether classmates liked or not(ß=0. 488, P<0. 001), be aware of the relationship with parents(ß=0. 201, P=0. 001), the power of the psychological resilience(ß=0. 046, P<0. 001) and the optimism of the psychological resilience(ß=-0. 030, P=0. 038), self-esteem(ß=-0. 140, P<0. 001). CONCLUSION: The depression symptoms of adolescents are related to many factors. The self-conscious teachers and classmates do not like himself(herself), and the bad relationship with parents are positively related to the depression symptoms of adolescents, while the psychological resilience and self-esteem are negatively related. The multi-level Model of repeated measurement is suitable for the analysis of the influencing factors and their changing rules in the longitudinal study of depression symptoms.

PDGF-BB/KLF4/VEGF Signaling Axis in Pulmonary Artery Endothelial Cell Angiogenesis.

BACKGROUND: Accumulating evidence suggests that platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor(VEGF) play a role in the progression of pulmonary arterial hypertension (PAH).Since chronic hypoxia is responsible for intimal hyperplasia and disordered angiogenesis of pulmonary arteries, which are histological hallmarks of PAH, we explored the role of the PDGF-BB/KLF4/VEGF signaling axis in the angiogenesis of pulmonary artery endothelial cells (PAECs). METHODS: Adult male Wistar rats were used to study hypoxia-induced or monocrotaline (MCT)-induced right ventricular (RV) remodeling as well as systolic function and hemodynamics using echocardiography and a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and RV vessels were performed. RESULTS: The results revealed that both the PDGF receptor-tyrosine kinase inhibitor imatinib and the multi-targeted VEGF and PDGF receptor inhibit or sunitinib malate reversed hypoxia-induced increases in right ventricular systolic pressure (RVSP), right ventricular function and thickening of the medial walls. Mechanistically VEGF/VEGFR and PDGF/PDGFR formed a biological complex. We also showed that PDGF-BBincreasedKLF4 promoter activity transcriptionally activating VEGF expression, which regulates PAEC proliferation; migration; and the cell-cycle transition from G0/G1phase to S phase and G2/M-phase and eventually leads to PAEC angiogenesis Conclusion: Our study indicates that hypoxia-induced angiogenesis of PAECs is associated with increased levels of PDGF-BB/KLF4/VEGF, which contribute to pulmonary vascular remodeling. Overall, our study contributes to a better understanding of PAH pathogenesis.

HPV11 E6 mutation by overexpression of APOBEC3A and effects of interferon-ω on APOBEC3s and HPV11 E6 expression in HPV11.HaCaT cells.

BACKGROUND: Condyloma acuminatum, infected by low-risk human papillomaviruses (e.g., HPV6 and HPV11), is one of the most widespread sexually transmitted diseases. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 proteins (APOBEC3s, A3s) are cellular cytidine deaminases acting as antiviral factors through hypermutation of viral genome. However, it remains unknown whether A3s results in HPV11 gene mutations and interferon-ω (IFN-ω) exhibits antiviral activities through the A3s system. Here we investigated whether enhanced APOBEC3A (A3A) resulted in the E6 gene mutations and explore the effects of recombinant human interferon-ω (rhIFN-ω) on A3s/E6 expression in HaCaT keratinocytes containing the genome of HPV 11 (HPV11.HaCaT cells). METHODS: A3A-overexpressed HPV11.HaCaT (A3A-HPV11.HaCaT) cells were established by lentiviral infection and verified by immunofluorescence and western-blotting. Cell cycle, E6 gene mutations, APOBEC3s/E6 gene expression and subcellular localization were detected by FACS, 3D-PCR and sequencing, qRT-PCR and immunofluorescence respectively. RESULTS: The results suggested that A3A-HPV11.HaCaT cells were successfully established. Enhanced A3A induced S-phase arrest, G > A/C > T mutations and obvious reduction of E6 mRNA expression. A3A/A3B mRNA expression was up-regulated at 6 h and 12 h and obvious A3A staining existed throughout HPV11.HaCaT cells after rhIFN-ω treatment. RhIFN-ω could also inhibit mRNA expression of HPV11 E6 significantly. CONCLUSIONS: Enhanced A3A repressed HPV11 E6 expression through gene hypermutation, and rhIFN-ω might be an effective agent against HPV11 infection by up-regulation of A3A.

Catalytic topological insulator Bi2Se3 nanoparticles for invivo protection against ionizing radiation.

Bi2Se3 nanoparticles (NPs) have attracted wide interests in biological and medical applications. Layer-like Bi2Se3 with high active surface area is promising for free radical scavenging. Here, we extended the medical applications of Bi2Se3 NPs further to in vivo protection against ionizing radiation based on their superior antioxidant activities and electrocatalytic properties. It was found that Bi2Se3 NPs can significantly increase the surviving fraction of mice after exposure of high-energy radiation of gamma ray. Additionally, the Bi2Se3 NPs can help to recover radiation-lowered red blood cell counts, white blood cell counts and platelet levels. Further investigations revealed that Bi2Se3 NPs behaved as functional free radical scavengers and significantly decreased the level of methylenedioxyamphetamine. In vivo toxicity studies showed that Bi2Se3 NPs did not cause significant side effects in panels of blood chemistry, clinical biochemistry and pathology.