Breaking the poverty trap in an ecologically fragile region through ecological engineering: A close-up look at long-term changes in ecosystem services.

Ecological vulnerability and poverty are interrelated and must be addressed together. The resolution of this issue will help us to meet the challenges during the process of implementing concrete actions for realizing the 2030 UN sustainable development goals (SDGs). Ecological restoration projects (ERPs) can enhance ecosystem services (ESs) while providing policy support for improving people's livelihoods. However, processes and mechanisms of ERPs on the ecological environment and socioeconomic development in poverty-stricken and ecologically fragile areas have rarely been studied. To address these issues, we conducted a comparative analysis on the changes of land use and land cover (LULC), ecosystem services (ESs), and socioeconomic development in Bijie City, a karst rocky desertification area in southwest China, before and after the implementation of ERPs in 2000, as well as the complex relationship between these factors. ERPs have affected LULCs, ESs, socioeconomics, and poverty reduction significantly since 2000. Specifically, the total ecosystem service value (ESV) in the study area has increased by more than 3 times in the past 30 years, with the ESV of tourism services and carbon storage increasing the most, from CNY 0.001 and 337.07 billion in 1990 to CNY 11.07 and 108.97 billion in 2019, respectively. The correlation between ESs is mainly synergistic, while the tradeoff between carbon storage and water yield is in a fluctuating upward trend. LULC conversion of cropland to green, and cropland to water, wetland and shrubs has positive effects on carbon storage and water yield, respectively. During study period, GDP, urbanization increased by over 70 times, 5 times, respectively, whereas poverty population, poverty incidence, and employment rate of various sectors (i.e., agriculture, forest, animal, and fishery, or AFAF) decreased by 96.4%, 97.7%, and 18.24%, respectively. Our findings emphasized that ERPs can effectively help poor and ecologically fragile areas to get out of the poverty trap and achieve the "win-win" goals of ecological and socio-economic sustainable development. These results have profound environmental management references to China and other developing countries around the world in realizing ecological restoration, poverty reduction, and the SDGs.

MiR-3960 inhibits bladder cancer progression via targeting of DEXI.

PURPOSE: MicroRNAs (miRNAs) are dominant cargo in exosomes and act as master regulators of cell function, inhibiting mRNA translation and affecting gene silencing. Some aspects of tissue-specific miRNA transport in bladder cancer (BC) and its role in cancer progression are not fully understood. MATERIALS AND METHODS: A microarray was used to identify miRNAs in mouse bladder carcinoma cell line MB49 exosomes. Real-time reverse transcription polymerase chain reaction was used to examine the expression of miRNAs in BC and healthy donor serum. Western blotting and immunohistochemical staining were used to examine the expression of dexamethasone-induced protein (DEXI) in patients with BC. CRISPR-Cas 9 was used to knock out Dexi in MB49, and flow cytometry was performed to test cell proliferation ability and apoptosis under chemotherapy. Human BC organoid culture, miR-3960 transfection, and 293T-exosome-loaded miR-3960 delivery were used to analyze the effect of miR-3960 on BC progression. RESULTS: The results showed that miR-3960 levels in BC tissue were positively correlated with patient survival time. Dexi was a major target of miR-3960. Dexi knockout inhibited MB49 cell proliferation and promoted cisplatin- and gemcitabine-induced apoptosis. Transfection of miR-3960 mimic inhibited DEXI expression and organoid growth. In parallel, 293T-exosome-loaded miR-3960 delivery and Dexi knockout significantly inhibited subcutaneous growth of MB49 cells in vivo. CONCLUSION: Our results demonstrate the potential role of miR-3960-mediated inhibition of DEXI as a therapeutic strategy against BC.

Pleural effusion caused by Trichinella spiralis infection: two case reports.

BACKGROUND: Trichinosis is a worldwide food-borne zoonotic parasitic disease, which is mainly obtained by ingesting undercooked meat containing infected larvae. The purpose of our article is to introduce and discuss two rare cases of pleural effusion caused by Trichinella spiralis. CASE PRESENTATION: Here we described two male patients who presented to the respiratory department of our hospital with a massive unilateral pleural effusion, their serum eosinophils were in the normal range, laboratory serological tests revealed that Trichinella spiralis IgG antibody was positive. After the oral administration of antiparasitic drugs, the pleural effusion of two patients was completely absorbed. CONCLUSION: Both patients were diagnosed with Trichinosis complicated with pleural effusion, which is very rare in the clinic and easy to be misdiagnosed because of normal eosinophils.

Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression.

BACKGROUND: The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) brings remarkable benefits for the survival of patients with advanced NSCLC harboring EGFR mutations. Unfortunately, acquired resistance seems to be inevitable and limits the application of EGFR-TKIs in clinical practice. This study reported a common molecular mechanism sustaining resistance and potential treatment options to overcome EGFR-TKIs resistance. METHODS: EGFR-TKIs resistant NSCLC cells were established and confirmed by MTT assay. Cholesterol content was detected and the promotional function of cholesterol on NSCLC growth was determined in vivo. Then, we identified ERRα expression as the downstream factor of cholesterol-mediated drug resistance. To dissect the regulatory mechanism, we conducted experiments, including immunofluorescence, co-immunoprecipitation, luciferase reporter assay and chromatin immunoprecipitation assay. RESULTS: Long-term exposure to EGFR-TKIs generate drug resistance with the characteristic of cholesterol accumulation in lipid rafts, which promotes EGFR and Src to interact and lead EGFR/Src/Erk signaling reactivation-mediated SP1 nuclear translocation and ERRα re-expression. Further investigation identifies ERRα as a target gene of SP1. Functionally, re-expression of ERRα sustains cell proliferation by regulating ROS detoxification process. Lovastatin, a drug used to decrease cholesterol level, and XCT790, an inverse agonist of ERRα, overcome gefitinib and osimertinib resistance both in vitro and in vivo. CONCLUSIONS: Our study indicates that cholesterol/EGFR/Src/Erk/SP1 axis-induced ERRα re-expression promotes survival of gefitinib and osimertinib-resistant cancer cells. Besides, we demonstrate the potential of lowing cholesterol and downregulation of ERRα as effective adjuvant treatment of NSCLC.

HPV16 E6 gene polymorphisms and the functions of the mutation site in cervical cancer among Uygur ethnic and Han nationality women in Xinjiang, China.

BACKGROUND: To investigate the genotype distribution of human papillomavirus (HPV) in infected Uygur and Han women in Xinjiang, China; analyze the HPV16 E6 gene polymorphism site and relationship with the development of cervical cancer. METHODS: The HPV16 E6 sequence was analyzed using the European standard prototype to perform an evolutionary tree. HPV16 E6-T295/T350, G295/G350, and T295/G350 GV230 vectors were stably transfected into cervical cancer C33A cells to analyze the cell proliferation, migration and invasion, apoptosis by CCK8 and clonogenic assays, transwell and cell scratch assays, FACS experiments. RESULTS: The total HPV infection rate was 26.390% (760/2879), whereas the Uygur 22.87% (196/857) and the Han was 27.89% (564/2022) (P < 0.05). Among 110 mutations, 65 cases of E6 genes were mutated at nucleotide 350 (T350G) with the leucine changing to valine (L83V). Moreover, there were 7 cases of E6 gene mutated at nucleotide 295 (T295G) with aspartic changing to glutamic (D64E). When E6 vector(s) of mutations sites were transfected into C33A cells, they were found to promote cellular proliferation, migration, invasion, and inhibit apoptosis. T295/G350-E6 was significantly stronger than G295/G350 and T295/T350, G295/G350 was significantly stronger than T295/T350 (P < 0.05). The T295/G350 had the strongest effect on C33A cells and G295/G350 was significantly stronger than T295/T350 (P < 0.05). CONCLUSIONS: The positive HPV infection rates differed between the Uygur and Han in Xinjiang, China, and the genotype distribution of infection was different. After transfecting C33A cells with different eukaryotic expression vectors, the T295/G350 mutation site promoted the proliferation, migration, and invasion of C33A cells to a greater extent than G295/G350; however, G295/G350 had a stronger effect than T295/T350.

Spatiotemporal distribution and risk assessment of organophosphorus pesticides in surface water and groundwater on the North China Plain, China.

90 groundwater samples and 14 surface water samples were collected in wet season (summer) and dry season (winter) in the North China Plain (NCP), and analyzed for 11 organophosphorus pesticides (OPPs). The results showed that the main types of OPPs in surface water and groundwater were dimethoate, dichlorvos, methyl-parathion, malathion in both summer and winter. The OPP concentrations in groundwater and surface water were higher in summer than in winter. In the vertical direction, the distribution characteristics of different four types of groundwater sampling points are different. In the horizontal direction: farmland adjacent to a river (FAR) > central farmland (CF) > nonfarm area adjacent to a river (NFAR) > central nonfarm area (CNF). The OPPs concentrations in surface water adjacent to farmland were higher than that in surface water adjacent to nonfarm area. The main factors influencing the distribution of OPPs in the groundwater and surface water were the interaction process between them, the groundwater flow field and the OPPs used in agricultural activities. The ecological risk of OPPs to surface water was greater in summer than in winter. Water Flea was at medium risk, and malathion had the greatest influence on Water Flea in both summer and winter. The non-carcinogenic and carcinogenic risks of the four main OPPs in surface water were higher than in groundwater, and were higher in summer than in winter, but they would not lead to adverse health effects on local residents.

Effect of allergic rhinitis on sleep in children and the risk factors of an indoor environment.

PURPOSE: Allergic rhinitis (AR) is an independent risk factor for sleep disorders in children, including abnormal sleep behaviors. We investigated the occurrence of abnormal sleep behaviors in children with AR to determine indoor environmental risk factors affecting sleep. METHODS: This case-control study collected the sleep status and characteristics of the indoor environment of children aged 3-14 years with and without AR using a questionnaire. The differences between the two groups were compared using the Mann-Whitney U test, chi-square test, and Fisher's exact test. The indoor environmental factors affecting sleep behavior were analyzed using logistic regression analysis. RESULTS: Children with AR (n=427) had a higher probability of snoring (8.7 % vs. 2.9 %; P < 0.001), mouth breathing (14.1 % vs. 5.2 %; P < 0.001), restless sleep (6.6 % vs. 4.1 %; P = 0.047), sleep talking (3.3 % vs. 1.1 %; P = 0.003), and hyperhidrosis (16.4 % vs. 8.5 %; P < 0.001) than those without AR (n=1046). Emulsion wall paint (odds ratio (OR) = 2.779; 95 % confidence interval (CI), 1.332-5.796; P = 0.006) and tobacco exposure in early infancy (OR = 2.065; 95 % CI 1.079-3.950; P = 0.029) were associated with hyperhidrosis. CONCLUSION: Children with AR are more likely to have abnormal sleep behaviors than those without, including snoring, mouth breathing, restless sleep, sleep talking, and hyperhidrosis. Emulsion paint wall and tobacco smoke exposure in early infancy had a twofold higher risk of hyperhidrosis during sleep.

Characteristics and risk factors of children with sleep-disordered breathing in Wuxi, China.

BACKGROUND: Sleep-disordered breathing (SDB) is a common syndrome in children, related to their immune responses, cardiovascular function, and neurocognitive function. This study aimed to determine the prevalence of SDB among children in Wuxi, China, and to evaluate the protective and risk factors of SDB in children. METHODS: A cross-sectional study was conducted on children attending different schools across Wuxi, China, aged 3-14 years old. Of a total of 5630 questionnaires distributed to the parents of the children, 3997 (71.0%) were deemed to be valid. The data on the general sociodemographic factors, children's allergy and sleep characteristics, and the parents' sleep characteristics were also collected. The Paediatric Sleep Questionnaire (PSQ) score was used to identify children at high risk of SDB. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. RESULTS: The prevalence of SDB in this cohort was 13.4% (N = 534). SDB prevalence significantly differed in children with asthma (28.2% vs. 12.8%, P < 0.001), eczema (19.0% vs. 10.0%, P < 0.001), urticaria (16.4% vs. 12.9%, P < 0.01) and rhinitis (21.4% vs. 10.7%, P < 0.001). No significant differences were found in SDB prevalence with respect to pillow material or quilt material. On multivariate logistic regression analysis, asthma (OR 1.986 (95% CI 1.312-3.007), P < 0.01), eczema (OR 1.675 (95% CI 1.377-2.037), P < 0.001), rhinitis (OR 1.998 (95% CI 1.635-2.441), suffered from familial sleep sickness (OR 2.416 (95% CI 1.975-2.955), P < 0.001) and whose mothers slept for a shorter duration (6 h-8 h: OR 1.370 (95% CI 1.089-1.724), P < 0.01; <6 h: OR 3.385(95% CI 2.098-5.461), P < 0.001) increased the odds of having SDB. The incidence of SDB significantly decreased with children's age (6-11 years old: 0R 0.768 (95% CI 0.597-0.989), P < 0.05; 12-14 years old: OR 0.691 (95% CI 0.530-0.901), P < 0.01). CONCLUSION: The results of this study demonstrated that atopic diseases (asthma, eczema, and rhinitis) and family sleep habits were risk factors for SDB in children in Wuxi, China.

Phosphorus deficiency induces root proliferation and Cd absorption but inhibits Cd tolerance and Cd translocation in roots of Populus × euramericana.

To disclose how phosphorus deficiency influence phytoremediation of Cd contamination using poplars, root architecture, Cd absorption, Cd translocation and antioxidant defense in poplar roots were investigated using a clone of Populus × euramericana. Root growth was unaltered by Cd exposure regardless of P conditions, while the degree of root proliferation upon P deficiency was changed by high level of Cd exposure. The concentration and content of Cd accumulation in roots were increased by P deficiency. This can be partially explained by the increased expression of genes encoding PM H + -ATPase under the combined conditions of P deficiency and high Cd exposure, which enhanced Cd2+-H+ exchanges and led to an increment of Cd uptake under P deficiency. Despite of the increasing Cd accumulation in roots, the translocation of Cd from roots to aerial tissues sharply decreased upon P deficiency. The relative expression of genes responsible for Cd translocation (HMA4) decreased upon P deficiency and thus inhibited Cd translocation via xylem. GR activity was decreased by P deficiency, which can inhibit the form of GSH and GSH-Cd complexes and decrease Cd translocation via GSH-Cd complexes. The transportation of PC-Cd complexes into vacuole decreased under P deficiency as a result of the low expression of PCS and ABCC1, and thus suppressed Cd tolerance and Cd detoxification in roots. Moreover, P deficiency decreased the levels of antioxidase (GR and CAT) and phytohormones including JA, ABA and GA3, which synchronously reduced antioxidant capacity in roots.

Genetic variations in E6, E7 and the long control region of human papillomavirus type 16 among patients with cervical lesions in Xinjiang, China.

BACKGROUND: Xinjiang is one of the areas with the highest incidence of cervical cancer in China. Genetic variation in Human papillomavirus type 16 (HPV16) may increase the ability of the virus to mediate carcinogenesis and immune escape, which are risk factors for the progression of cervical cancer. We investigated polymorphism in HPV16 and the distribution of its sub-lineages in the region by analyzing the E6, E7 and long control region (LCR) gene sequences from women with HPV16-positive cervical samples in Xinjiang. METHODS: A total of 138 cases of cervical lesions and squamous cell carcinoma with infection of HPV16 virus were collected. The E6 and E7 genes and LCR of HPV16 virus were sequenced and compared with the HPV16 European prototype reference and other HPV16 mutants for single nucleotide polymorphisms. Neighbor-joining phylogenetic trees were constructed using E6, E7 and LCR sequences. RESULTS: Fourteen missense mutations were found in the E6 gene; the loci with the highest mutation frequency were T350G (36/75, 48%) and T178G (19/75, 25.3%). In the E7 gene, the locus with the highest mutation frequency was A647G (18/75, 24%). A total of 33 polymorphic sites were found in the LCR, of which T7447C (39/95, 40.1%) was the most frequent. CONCLUSION: HPV16 in Xinjiang is mainly of the European variant, followed by the Asian variant type; no Africa 1, 2 or Asia-America variant types were found.

High cholesterol in lipid rafts reduces the sensitivity to EGFR-TKI therapy in non-small cell lung cancer.

Overcoming EGFR-TKI resistant which has the initial enthusiasm over substantial clinical responses is a formidable challenge on nowadays. In this study, we showed that cholesterol level in lipid rafts in gefitinib resistant non-small cell lung cancer (NSCLC) cell lines was remarkably higher than gefitinib sensitive cell line, and depletion of cholesterol increased gefitinib sensitivity. Furthermore, cholesterol-depleted enhanced gefitinib inhibit phosphorylation of EGFR, Akt-1, MEK1/2, and ERK1/2 and these were reversed in cholesterol add-back experiments. Gefitinib resistant cell lines showed high affinity of gefitinib and EGFR when cholesterol was depleted. Therefore, targeting cholesterol combined with EGFR-TKI is potentially a novel therapeutic strategy for gefitinib resistant treatment.

MiR-544 promotes immune escape through downregulation of NCR1/NKp46 via targeting RUNX3 in liver cancer.

OBJECTIVE: To study the potential role of miR-544 in the immune escape mechanism of hepatoma cells. METHODS: Natural killer (NK) cells were collected from healthy volunteers and patients with liver cancer. Interleukin (IL)-2 activated-NK-92 cells were transfected with miR-544 inhibitor/mimic or NC/pre-NC in HepG2 co-culture system. NK-92 cells were treated with control, IL-2, IL-2 + pre-NC, IL-2 + miR-544 mimic, IL-2 + miR-544 mimic + pcDNA and IL-2 + miR-544 mimic + pcDNA-runt-related transcription factor 3 (RUNX3) groups. Mice models of liver cancer were well established. Expression of miR-544, natural cytotoxicity receptor 1 (NCR1) and RUNX3 were evaluated by quantitative real-time PCR and western blotting. Flow cytometry and ELISA were used to determine NK cell cytotoxicity and the levels of INF-γ, respectively. RESULTS: MiR-544 was upregulated while NCR1 and RUNX3 was downregulated in NK cells of patients with liver cancer. The levels of IFN-γ and miR-544 expression were increased and decreased in IL-2 activated-NK cells, respectively. Inversely, miR-544 overexpression inhibited NK cell cytotoxicity by downregulating IFN-γ. However, miR-544 directly targeted RUNX3 and negatively regulated NCR1. Furthermore, miR-544 promoted immune escape of hepatoma cells in vivo and in vitro. CONCLUSION: miR-544 promoted the immune escape of liver cancer cells by downregulating NCR1 via targeting RUNX3.

TIPE3 differentially modulates proliferation and migration of human non-small-cell lung cancer cells via distinct subcellular location.

BACKGROUND: TIPE3 (TNFAIP8L3), a transfer protein for lipid second messengers, is upregulated in human lung cancer tissues. The most popular lung cancer is non-small cell lung cancer (NSCLC) with high incidences and low survival rates, while the roles of TIPE3 in NSCLC remain largely unknown. METHODS: TIPE3 expression was examined in tissue chips from patients with NSCLC using immunohistochemistry; the correlation of plasma membrane expression of TIPE3 with T stage of NSCLC was analyzed. After endogenous TIPE3 was silenced via siRNA, or TIPE3 with N or C-terminal flag was overexpressed via transient or stable transfection, human NSCLC cells were assayed for the proliferation and migration, respectively. NSCLC cells, in which TIPE3 with C-terminal flag was stably transfected, were inoculated into mice to establish xenograft tumors, the tumor growth and the expression of TIPE3 in tumor tissues were examined. RESULTS: TIPE3 was broadly expressed in lung tissues of patients with NSCLC. The plasma membrane expression of TIPE3 was positively correlated with the T stage of NSCLC. Knockdown of endogenous TIPE3, which was predominantly expressed in the plasma membrane, inhibited the proliferation and migration of NSCLC cells. While transient overexpression of TIPE3 with N-terminal flag, which was mostly trapped in the cytoplasm, inhibited the growth and migration of NSCLC cells accompanied by inactivation of AKT and ERK. In contrast, stable overexpression of TIPE3 with C-terminal flag, which could be localized in the plasma membrane, markedly promoted the growth and migration of NSCLC cells through activation of AKT and ERK. Notably, in xenograft tumor models established with NSCLC cells, stable overexpression of TIPE3 with C-terminal flag in NSCLC cells significantly promoted the tumor growth and enhanced the expression and plasma membrane localization of TIPE3 in tumor tissues. CONCLUSION: This study demonstrates that human TIPE3 promotes the proliferation and migration of NSCLC cells depending on its localization on plasma membrane, whereas cytoplasmic TIPE3 may exert a negative function. Thus, manipulating the subcellular location of TIPE3 can be a promising strategy for NSCLC therapy.

Methylation in the promoter regions of WT1, NKX6-1 and DBC1 genes in cervical cancer tissues of Uygur women in Xinjiang.

This study aimed to explore: 1) DNA methylation in the promoter regions of Wilms tumor gene 1 (WT1), NK6 transcription factor related locus 1 gene (NKX6-1) and Deleted in bladder cancer 1 (DBC1) gene in cervical cancer tissues of Uygur women in Xinjiang, and 2) the correlation of gene methylation with the infection of HPV16/18 viruses. We detected HPV16/18 infection in 43 normal cervical tissues, 30 cervical intraepithelial neoplasia lesions (CIN) and 48 cervical cancer tissues with polymerase chain reaction (PCR) method. Methylation in the promoter regions of the WT1, NKX6-1 and DBC1 genes in the above-mentioned tissues was measured by methylation-specific PCR (MSP) and cloning sequencing. The expression level of these three genes was measured by real-time PCR (qPCR) in 10 methylation-positive cervical cancer tissues and 10 methylation-negative normal cervical tissues. We found that the infection of HPV16 in normal cervical tissues, CIN and cervical cancer tissues was 14.0, 36.7 and 66.7%, respectively. The infection of HPV18 was 0, 6.7 and 10.4%, respectively. The methylation rates of WT1, NKX6-1 and DBC1 genes were 7.0, 11.6 and 23.3% in normal cervical tissues, 36.7, 46.7 and 30.0% in CIN tissues, and 89.6, 77.1 and 85.4% in cervical cancer tissues. Furthermore, WT1, NKX6-1 and DBC1 genes were hypermethylated in the high-grade squamous intraepithelial lesion (CIN2, CIN3) and in the cervical cancer tissues with infection of HPV16/18 (both P< 0.05). The expression of WT1, NKX6-1 and DBC1 was significantly lower in the methylation-positive cervical cancer tissues than in methylation-negative normal cervical tissues. Our findings indicated that methylation in the promoter regions of WT1, NKX6-1 and DBC1 is correlated with cervical cancer tumorigenesis in Uygur women. The infection of HPV16/18 might be correlated with methylation in these genes. Gene inactivation caused by methylation might be related to the incidence and development of cervical cancer.

Imperatorin acts as a cisplatin sensitizer via downregulating Mcl-1 expression in HCC chemotherapy.

Acquisition of cisplatin resistance is the common and critical limitation for hepatocellular carcinoma (HCC) therapy. Our study was aimed to determine whether there were conditions under which the addition of imperatorin would reverse the resistance of HCC cells to cisplatin-based therapy. In this study, we found that addition of imperatorin significantly enhanced the cytotoxicity of cisplatin to HCC cells. Since the Mcl-1 was overexpressed in HCC cell lines (HepG2, HepG3B, PLC, Huh7) compared with normal liver cell line (L-O2), we found that the Mcl-1 expression was downregulated by imperatorin but not influenced by cisplatin in HCC cells. In addition, our results showed the combination of imperatorin and cisplatin induced apoptosis and ∆Ψm collapse more significantly compared with treatment of imperatorin or cisplatin alone. Furthermore, the imperatorin-induced sensitization for cisplatin-cytotoxicity to HCC cells was abolished by the transfection of Mcl-1 expression plasmid. Finally, we found that the addition of imperatorin significantly reversed the resistance to cisplatin in cisplatin-resistant HCC cells, which was Mcl-1 dependent. In summary, our study revealed that combination with imperatorin could enhance the antitumor activity of cisplatin via targeting Mcl-1 and reverse the resistance to cisplatin in HCC.

Nuclear-targeting TAT-PEG-Asp8-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer.

AIM: Drug efflux-associated multidrug resistance (MDR) is a main obstacle to effective cancer chemotherapy. Large molecule drugs are not the substrates of P-glycoprotein, and can circumvent drug efflux and be retained inside cells. In this article we report a polymer-drug conjugate nanoparticulate system that can overcome MDR based on size-related exclusion effect. METHODS: Doxorubicin was coupled with the triblock polymeric material cell-penetrating TAT-PEG-poly(aspartic acid). The amphiphilic macromolecules (termed TAT-PEG-Asp8-Dox) could self-assemble into nanoparticles (NPs) in water. The antitumor activity was evaluated in drug-resistant human colon cancer HCT8/ADR cells in vitro and in nude mice bearing HCT8/ADR tumor. RESULTS: The self-assembling TAT-PEG-Asp8-Dox NPs were approximately 150 nm with a narrow particle size distribution, which not only increased the cellular uptake efficiency, but also bypassed P-glycoprotein-mediated drug efflux and improved the intracellular drug retention, thus yielding an enhanced efficacy for killing drug-resistant HCT8/ADR colon cancer cells in vitro. Importantly, the TAT-PEG-Asp8-Dox NPs enhanced the intranuclear disposition of drugs for grater inhibition of DNA/RNA biosynthesis. In nude mice bearing xenografted HCT8/ADR colon cancers, intravenous or peritumoral injection of TAT-PEG-Asp8-Dox NPs for 22 d effectively inhibited tumor growth. CONCLUSION: TAT-PEG-Asp8-Dox NPs can increase cellular drug uptake and intranuclear drug delivery and retain effective drug accumulation inside the cells, thus exhibiting enhanced anticancer activity toward the drug-resistant human colon cancer HCT8/ADR cells.

[Roles of histone acetyltransferase and histone deacetylase in the pathogenesis of bronchial asthma].

OBJECTIVE: To evaluate the roles of various cytokines, histone acetyltransferase (HAT) and histone deacetylase (HDAC) in the pathogenesis of bronchial asthma. METHODS: BALB/C mice were randomly assigned to control, untreated asthma, hormone treatment and TSA treatment groups. Bronchial asthma was induced by intraperitoneal injections and atomization inhalation of ovalbumin (OVA) in the asthma, hormone treatment and trichostatin (TSA) treatment groups. The mice in the hormone treatment and TSA treatment groups were administered with dexamethasone 1.0 mg/kg and TSA 1.0 mg/kg respectively by an intraperitoneal injection 30 minutes before challenge of asthma. At 24 hours after the last challenge, IL-4, IL-8 and IFN- levels in serum were measured using ELISA, and activities of HAT and HDAC in peripheral blood mononuclear cells (PBMC) were determined by the enzyme linked immunofluorescence assay. RESULTS: The serum levels of IL-4 and IL-8 in the untreated asthma group were higher than in the control, hormone treatment and TSA treatment groups (P<0.05). There was no difference in the serum levels of IL-4 and IL-8 among the control, hormone treatment and TSA treatment groups (P>0.05). The activity of HDAC in the untreated asthma group was lower than in the control, hormone treatment and TSA treatment groups (P<0.05). Hormone treatment significantly decreased the activity of HAT compared with the untreated asthma group (P<0.05). There was no difference in the activities of HAT and HDAC among the control, hormone treatment and TSA treatment groups (P>0.05). CONCLUSIONS: The decreased activity of HDAC leads to an increased secretion of inflammatory factors and thus induces asthma.

Development of determination of four analytes of Zhi-Shao-San decoction using LC-MS/MS and its application to comparative pharmacokinetics in normal and irritable bowel syndrome rat plasma.

Zhi-Shao-San (ZSS), a traditional Chinese medicinal prescription, has been clinically used for the treatment of irritable bowel syndrome (IBS) for centuries. A comparative study was designed and conducted to compare the pharmacokinetic differences between paeoniflorin naringin, hesperidin and neohesperidin after oral administration of ZSS decoction to normal rats and IBS rats induced by acetic acid and restraint stress. Further, an efficient, sensitive and selective liquid chromatography/tandem mass spectrometry for the simultaneous determination of four analytes of ZSS decoction in rat plasma was developed and validated. The validated method was successfully applied to comparison of pharmacokinetic profiles of analytes in rat plasma. The results showed that the absorptions of naringin, hesperidin and neohesperidin in IBS group were all significantly higher than those in normal group and no obvious difference was seen for paeoniflorin between the two groups, which is helpful for improving clinical therapeutic efficacy and further pharmacological studies of ZSS.

[Roles of CD4+CD25+Foxp3+ regulatory T cells and IL-33 in the pathogenesis of asthma in children].

OBJECTIVE: To study the roles of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) and IL-33 in the pathogenesis of asthma in children. METHODS: Flow cytometry was used to detect peripheral blood CD4(+)CD25(+)Foxp3(+)Treg proportion in CD4(+)T lymphocytes in.45 children with asthma, 50 children with wheezing caused by respiratory syncytial virus infection and 40 healthy children. Serum levels of IFN-γ, IL-4, IL-5 and IL-33 were measured using ELISA. RESULTS: The level of peripheral blood CD4(+)CD25(+)Foxp3(+)Treg in the asthma group was significantly lower than in the wheezing and control groups (P<0.05). In contrast, serum levels of IL-33 in the asthma group was significantly higher than in the wheezing and control groups (P<0.05). Peripheral blood CD4(+)CD25(+)Foxp3(+)Treg level was negatively correlated with serum IL-33 level in the asthma group(r=-0.156, P<0.01). CONCLUSIONS: CD4(+)CD25(+)Foxp3(+)Treg may interact with IL-33 in the pathogenesis of childhood asthma.

The application of graphic language personalized emotion in graphic design.

Emotion Recognition is the experience of attitude in graphic language expression and composition. People use both verbal and non-verbal behaviours to communicate their emotions. Visual communication and graphic design are always evolving to meet the demands of an increasingly affluent and culturally conscious populace. When graphic designing works, designers should consider their own opinions about related works from the audience's or customer's standpoint so that the emotion between them can resonate. Hence, this study proposes a personalized emotion recognition framework based on convolutional neural networks (PERF-CNN) to create visual content for graphic design. Graphic designers prioritize the logic of showing objects in interactive designs and use visual hierarchy and page layout approaches to respond to users' demands via typography and imagery. This ensures that the user experience is maximized. This research identifies three tiers of emotional thinking: expressive signal, emotional experience, and emotional infiltration, all of which affect graphic design. This article explores the subject of graphic design language and its ways of emotional recognition, as well as the relationship between graphic images, shapes, and feelings. CNN initially extracted expressive features from the user's face images and the poster's visual information. The clustering process categorizes the poster or advertisement images into positive, negative, and neutral classes. Research and applications of graphic design language benefit from the proposed method's experimental results, demonstrating that it outperforms conventional classification approaches in the dataset. In comparison to other popular models, the experimental results demonstrate that the proposed PERF-CNN model improves each of the following: classification accuracy (97.4 %), interaction ratio (95.6 %), emotion recognition ratio (98.9 %), rate of influence of pattern and colour features (94.4 %), and prediction error rate (6.5 %).