Imidacloprid affects human cells through mitochondrial dysfunction and oxidative stress.

Given their relatively low persistence and mammalian toxicity, neonicotinoid pesticides have been extensively used worldwide and are omnipresent in the environment. Recent studies have shown that neonicotinoids may pose adverse effects on non-target organisms other than the known neurotoxicity, raising emerging concerns that these insecticides might pose human health risk through additional toxicity pathways. In the present study, the mitochondria function, oxidative stress, DNA damages, and genes transcription levels were examined in the human neuroblastoma SH-SY5Y cells after 48-h exposure to imidacloprid at concentrations from 0.05 to 200 µmol/L. Results showed that imidacloprid induced mitochondrial dysfunction with the degradation of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) levels. In addition, imidacloprid caused oxidative stress by stimulating the generation of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) via the disruption of calcium ion level and mitochondrial function. Ultimately, the oxidative stress continued to produce DNA damage and apoptosis in SH-SY5Y cells at imidacloprid concentrations above 47.6 µmol/L. Among the evaluated endpoints, ATP was the most sensitive, with a median activity concentration of 0.74 µmol/L. The 5 % hazard concentration of imidacloprid was estimated to be 0.69 µmol/L, which can be used as a threshold for human health risk assessment for imidacloprid. Collectively, our results provide an important support for further research on potential toxicity of neonicotinoids related to mitochondrial toxicity in humans.

A critical review of distribution, toxicological effects, current analytical methods and future prospects of synthetic musks in aquatic environments.

Synthetic musks (SMs) have gained widespread utilization in daily consumer products, leading to their widespread dissemination in aquatic environments through various pathways. Over the past few decades, the production of SMs has consistently risen, prompting significant concern over their potential adverse impacts on ecosystems and human health. Although several studies have focused on the development of analytical techniques for detecting SMs in biological samples and cosmetic products, a comprehensive evaluation of their global distribution in diverse aquatic media and biological matrices remains lacking. This review aims to provide an up-to-date overview of the occurrence of SMs in both aquatic and various biological matrices, investigating their worldwide distribution trends, assessing their ecological toxicity, and comparing different methodologies for processing and analysis of SMs. The findings underscore the prevalence of polycyclic musks as predominant SMs, with consumption of various products in different countries leading to contrasting distribution of contaminants. Furthermore, the migration of SMs from sediments to the water phase is investigated, indicating the role of solid-phase reservoirs. Incomplete degradation of SMs in the environment could contribute to their accumulation in aquatic systems, impacting the growth and oxidative stress of aquatic organisms, and having a possibility of genotoxicity to them. Human exposure data highlight substantial risks for vulnerable populations such as pregnant women and infants. Moreover, contemporary methods for SMs analysis are presented in this review, particularly focusing on advancements made in the last five years. Finally, research enhancement and critical questions regarding the analysis of SMs are provided, offering suggestions for future research endeavors.

Occurrence, distribution, and translocation of legacy and current-use pesticides in pomelo orchards in South China.

Pomelo (Citrus grandis) is a highly popular and juicy member of the citrus family. However, little is known regarding the occurrence and distribution of pesticides in pomelo. In this study, we determined the levels of legacy (n = 25) and current-use pesticides (n = 2) in all parts of pomelo (i.e., epicarp, mesocarp, endocarp, pulp, and seed) and paired soil and leaf samples collected from two pomelo orchards in South China. At least one target pesticide was detected in the pomelo fruit, soil, and leaf samples, indicating that these pesticides were ubiquitous. The spatial distribution of the total concentration of pesticides in the pomelo parts was in the order of epicarp (216 ng/g) > mesocarp (9.50 ng/g) > endocarp (4.40 ng/g) > seed (3.80 ng/g) > pulp (1.10 ng/g), revealing different spatial distributions in pomelo. Principal component analysis was performed based on the concentrations of the target pesticides in the pulp and paired samples of epicarp, leaf, topsoil, and deep soil to examine the translocation pathway of the pesticides in pomelo. Close correlations were found among the target pesticides, and the pesticides in the pulp were mainly transferred from the epicarp, topsoil, or deep soil. We also explored the factors that affected such transport and found that the main translocation pathway of the non-systemic pesticide (i.e., buprofezin) into the pulp was the epicarp, whereas the systemic pesticide (i.e., pyriproxyfen) was mainly derived from the soil. The cumulative chronic dietary risks of all the pesticides resulting from pomelo consumption were much lower than the acceptable daily intake values for the general population. However, the prolonged risk of exposure to these pesticides should not be underestimated. The potential health risks posed by legacy and current-use pesticides, which are widely and frequently utilized, should be given increased attention.

Target immune components to circumvent sorafenib resistance in hepatocellular carcinoma.

Sorafenib, a multi-kinase inhibitor, has been approved for cancer treatment for decades, especially hepatocellular carcinoma (HCC). Although sorafenib produced substantial clinical benefits in the initial stage, a large proportion of cancer patients acquired drug resistance in subsequent treatment, which always disturbs clinical physicians. Cumulative evidence unraveled the underlying mechanism of sorafenib, but few reports focused on the role of immune subpopulations, since the immunological rationale of sorafenib resistance has not yet been defined. Here, we reviewed the immunoregulatory effects of sorafenib on the tumor microenvironment and emphasized the potential immunological mechanisms of therapeutic resistance to sorafenib. Moreover, we also summarized the clinical outcomes and ongoing trials in combination of sorafenib with immunotherapy, highlighted the immunotherapeutic strategies to improve sorafenib efficacy, and put forward several prospective questions aimed at guiding future research in overcoming sorafenib resistance in HCC.

Trends and Challenges Regarding the Source-Specific Health Risk of PM2.5-Bound Metals in a Chinese Megacity from 2014 to 2020.

Identifying the health risk of PM2.5 is essential for urban air pollution control. In 2013, China announced the ever-strict national Air Pollution Prevention and Control Action Plan, and its health benefit should be evaluated to provide reference for future policymaking. In this study, we conducted a seven-year (2014-2020) continuous observation of PM2.5 in Shenzhen, the third largest city in China, which has relatively good air quality. The results showed that the annual mean PM2.5 and total concentration of 21 associated metals dropped from 37.7 to 18.5 µg/m3 and from 2.4 to 1.1 µg/m3, respectively. Combining methods for source apportionment and health risk assessment, we found that the total carcinogenic risk (CR) of five hazardous metals (Cd, Cr, Ni, Co, and Pb) showed a clear decreasing trend. However, the total CR (1.8 × 10-6) in 2020 still exceeded the widely acceptable risk level (i.e., 1 × 10-6), with the primary contributor changing from industrial emissions (61%) to vehicle emissions (63%). Further analysis indicated that the CR of vehicles mainly came from Cr and Ni released by braking and tire wearing and has fluctuated in recent years, highlighting a great challenge of controlling nonexhaust emissions of vehicles (including electric cars) in the future.

Soil dust as a potential bridge from biogenic volatile organic compounds to secondary organic aerosol in a rural environment.

The role of coarse particles has recently been proven to be underestimated in the atmosphere and can strongly influence clouds, ecosystems and climate. However, previous studies on atmospheric chemistry of volatile organic compounds (VOCs) have mostly focused on the products in fine particles, it remains less understood how coarse particles promote secondary organic aerosol (SOA) formation. In this study, we investigated water-soluble compounds of size-segregated aerosol samples (0.056 to >18 µm) collected at a coastal rural site in southern China during late summer and found that oxygenated organic matter was abundant in the coarse mode. Comprehensive source apportionment based on mass spectrum and 14C analysis indicated that different from fossil fuel SOA, biogenic SOA existed more in the coarse mode than in the fine mode. The SOA in the coarse mode showed a unique correlation with biogenic VOCs. 13C and elemental composition strongly suggested a pathway of heterogeneous reactions on coarse particles, which had an abundant low-acidic aqueous environment with soil dust to possibly initiate iron-catalytic oxidation reactions to form SOA. This potential pathway might complement understanding of both formation of biogenic SOA and sink of biogenic VOCs in global biogeochemical cycles, warrantying future relevant studies.

Atmospheric ozonolysis of crotonaldehyde in the absence and presence of hydroxylated silica oligomer cluster adsorption.

As one of the main components of combustion of tobacco products occurs (CARB), crotonaldehyde has an acute toxicity and widely exists in the atmosphere, which is harmful to human health. The removal efficiency of VOCs by ozonation can reach 80-90%. Based on the theory of quantum chemistry, the degradation mechanism, kinetics and toxicity of crotonaldehyde by ozonation in gas phase and heterogeneous phase were studied. Ozone was added to the olefins unsaturated double bond to form a five-membered ring primary ozonide, which was further fractured due to its unstable structure to form a Criegee intermediate and an aldehyde compound. The reaction rate constant of crotonaldehyde with ozone was 1.24 × 10-17 cm3 molecule-1 s-1 at 298 K and 1 atm, which was an order of magnitude higher than the experimental value. From toxicity assessment, it was found that the ozonation of crotonaldehyde is beneficial to the removal of toxicity. Mineral dust aerosol exists in the atmosphere in large quantities, and SiO2 is the most abundant component. VOCs are transformed into particle state on their surface through homogeneous nucleation and heterogeneous nucleation. Referring to the crystal structure of SiO2, five hydroxylated silica oligomer cluster structures were simulated and the adsorption configurations of crotonaldehyde on their surface were simulated. The adsorption of crotonaldehyde on the surface of the clusters was achieved by forming hydrogen bonds and had good adsorption effects. The adsorption of hydroxylated silica oligomer clusters didn't change the ozonation mechanism of crotonldehyde, but had a certain effect on the reaction rate.

Effects of sulfometuron-methyl on zebrafish at early developmental stages.

Sulfometuron methyl (SM) is a widely used herbicide and thus leading to accumulation in the environment. The toxicity assessments of SM in model organisms are currently rare. In the present study, zebrafish were utilized for evaluating the detrimental effects of SM in aquatic vertebrates. Zebrafish embryos were exposed to 0, 10, 20, and 40 mg/L SM from 5.5 to 72 h post-fertilization (hpf), respectively. Consequently, SM exposure resulted in increasing the mortality rate and reducing hatching rate in larval zebrafish at 10, 20, and 40 mg/L SM-treated groups. The reduced numbers of immune cells (neutrophils and macrophages) were observed after SM exposure by a dose-dependent manner. The inflammatory responses (TLR4, MYD88, IL-1ß, IL-6, IL-8, IFN-γ, IL-10, and TGF-ß) were measured to estimate immune responses. Anti-inflammatory factors (IL-10 and TGF-ß) were down-regulated in all the treated groups and significantly altered at 40 mg/L exposure group. Additionally, behavioral tests suggested that SM treatment significantly increased the total distance, average speed, and maximum acceleration of larval zebrafish during light-dark transition and subsequently enzymology test displayed the same trend to locomotor behaviors. The content significantly increased in oxidative stress, as reflected in ROS level in all the treated groups. The numbers of cell apoptosis were significantly increased at 20, and 40 mg/L and the highest concentration group induced the substantial increment (P < 0.001) of apoptosis-related genes including p53, Bax/Bcl-2, caspase-9, and caspase-3. In summary, our results demonstrated that exposure to SM caused toxicity of development, immune system, locomotor behavior, oxidative stress, and cell apoptosis at the early developmental stages of zebrafish.

Joint toxicity of imidacloprid and azoxystrobin to Chironomus dilutus at organism, cell, and gene levels.

Pesticides occur in the environment as mixtures, yet the joint toxicity of pesticide mixtures remains largely under-explored and is usually overlooked in ecological risk assessment. In the current study, joint toxicity of a neonicotinoid insecticide (imidacloprid, IMI) and a strobilurin fungicide (azoxystrobin, AZO) was investigated with Chironomus dilutus over a wide range of concentrations and at different effect levels (organism, cell, and gene levels). The two pesticides, both individually and in combination, were found to induce oxidative stress and cause lethality in C. dilutus. Median lethal concentrations for IMI and AZO were 3.98 ± 1.17 and 52.9 ± 1.1 µg/L, respectively. Mixtures of the two pesticides presented synergetic effects at environmentally relevant concentrations whilst antagonistic effects at high concentrations, showing concentration-dependent joint toxicity. Investigation on the expressions of 12 genes (cyt b, coi, cox1, cyp4, cyp12m1, cyp9au1, cyp6fv1, cyp315, gst, Zn/Cu-sod, Mn-sod, and cat) revealed that the two pesticides impaired mitochondrial respiration, detoxification, and antioxidant system of C. dilutus, and the joint effects of the two pesticides were likely due to an interplay between their respective influences on these physiological processes. Collectively, the synergistic effects of the two pesticides at environmentally relevant concentrations highlight the importance to incorporate combined toxicity studies into ecological risk assessment of pesticides.

Theoretical Study of Ozonation of Methylparaben and Ethylparaben in Aqueous Solution.

Parabens are widely employed in toothpaste, cosmetics, textiles, beverages, and preservatives, causing a serious environmental concern because they are endocrine-disrupting compounds (EDCs). As one of the highly reactive oxidants, ozone has a great effect on EDC removal. To understand the degradation and transformation of parabens in the aquatic environment and their toxicity to aquatic organisms, the degradation reaction of parabens initiated by O3 was studied meticulously using quantum chemical calculations. The degradation process includes multiple initial reaction channels and consequent degradation pathways of the Criegee intermediates. Through thermodynamic data, the rate constants were computed using the transition state theory (TST). At a temperature of 298 K and a pressure of 1 atm, the calculated rate constants were 3.92 and 3.94 M-1 s-1 for methylparaben (MPB) and ethylparaben (EPB), respectively. The rate constants increased as the temperature increased or as the length of the alkyl chain on the benzene ring increased. Through the ecotoxicity assessment procedure, the ecotoxicity of parabens and the products in the degradation process can be assessed. Most degradation byproducts are either less toxic or nontoxic. Some byproducts are still harmful, such as oxalaldehyde (P2) and ethyl 2,3-dioxopropanoate (P10). Furthermore, the ecological toxicity of parabens increased with augmentation of the alkyl chain on the benzene ring. The effect of the alkyl chain length on the benzene ring in the compound cannot be ignored.

Ozonation of diclofenac in the aqueous solution: Mechanism, kinetics and ecotoxicity assessment.

The pharmaceutical and personal care products (PPCPs) in aquatic environment have aroused more interest recently. Many of them are hard to degrade by the typical biological treatments. Diclofenac (DCF), as a significant anti-inflammatory drug, is a typical PPCP and widely existed in water environment. It is reported that DCF has adverse effects on aquatic organisms. This work aims to investigate the mechanism, kinetics and ecotoxicity assessment of DCF transformation initiated by O3 in aqueous solution, and provide a solution to the degradation of DCF. The O3-initiated oxidative degradations of DCF were performed by quantum chemical calculations, including thirteen primary reaction pathways and subsequent reactions of the Criegee intermediates with H2O, NO and O3. Based on the thermodynamic data, the kinetic parameters were calculated by the transition state theory (TST). The total reaction rate constant of DCF initiated by O3 is 2.57 × 103 M-1 s-1 at 298 K and 1 atm. The results show that the reaction rate constants have a good correlation with temperature. The acute and chronic toxicities of DCF and its degradation products were evaluated at three different trophic levels by the ECOSAR program. Most products are converted into less toxic or harmless products. Oxalaldehyde (P3) and N-(2,6-dichlorophenyl)-2-oxoacetamide (P6) are still harmful to the three aquatic organisms, which should be paid more attention in the future.

Up-regulation of miR-139-5p protects diabetic mice from liver tissue damage and oxidative stress through inhibiting Notch signaling pathway.

The occurrence and development of diabetes seriously threaten the health of patients. Therefore, the mechanism exploration of diabetes is of great significance for more effective control of this disease. In this study, we aimed to investigate the regulatory mechanism of miR-139-5p and Notch signaling pathway on liver damage and oxidative stress in diabetic mice. The mouse model of diabetes was established, and the mice were divided into normal group, model group, negative control (NC) group, miR-139-5p mimic group, miR-139-5p inhibitor group, DAPT group, and miR-139-5p inhibitor + DAPT group. The mRNA expressions of miR-139-5p, Notch1, Jagged1, and NICD1, and the protein expressions of Notch1, Jagged1, and NICD1 were detected. In addition, HepG2 cells were cultured for high glucose induction, and cell cycle distribution and apoptosis were detected by flow cytometry. The results showed that the body weights of mice in the model, NC, miR-139-5p mimic, miR-139-5p inhibitor, DAPT, and miR-139-5p inhibitor + DAPT groups were all lower than that in the normal group. Co-localization of miR-139-5p and Notch1 was observed in the fluorescence in situ hybridization assay, and miR-139-5p was found to negatively regulate Notch1. Furthermore, reduced blood glucose level and inhibited liver oxidative stress were observed in mice with miR-139-5p overexpression or DAPT treatment. DAPT treatment reversed the increase of blood glucose level and oxidative stress injury caused by miR-139-5p silencing. In conclusion, up-regulation of miR-139-5p expression can protect liver tissue from oxidative stress injury in diabetic mice, and its mechanism may be related to the inhibition of Notch signaling pathway.

Transcriptomic analysis reveals common pathways and biomarkers associated with oxidative damage caused by mitochondrial toxicants in Chironomus dilutus.

A variety of chemicals are capable of provoking mitochondrial dysfunction and thereby contribute to metabolic disorder related effects in wildlife and human. For better identifying new mitochondrial toxicants and assessing mitochondria-related risk, an in-depth understanding of toxic mechanisms and biomarkers should be attained. In the current study, a representative mitotoxicant, azoxystrobin, was assessed for lethal and sublethal outcomes in Chironomus dilutus after 96-h exposure and the toxic mechanism was explored. Global transcriptomic profiles by RNA-sequencing revealed that ampk, acc1, atp2a, gsk3b, pi3k, fak, atr, chk1, and map3k5 were the key genes which involved in the toxic action of azoxystrobin and could serve as potential molecular biomarkers. A major network of common toxicity pathways was then developed for mitotoxicants towards aquatic insects. In particular, calcium ion-PI3K/AKT and cAMP-AMPK-lethality pathways were demonstrated, in addition to the well-known mitochondrial electron transfer-oxidative damage-apoptosis pathway. These analyses could help developing adverse outcome pathways that integrate toxicological information at various levels and support more effective risk assessment and management of mitotoxicants.

Toxicogenomics provides insights to toxicity pathways of neonicotinoids to aquatic insect, Chironomus dilutus.

Neonicotinoid insecticides have posed a great threat to non-target organisms, yet the mechanisms underlying their toxicity are not well characterized. Major modes of action (MoAs) of imidacloprid were analyzed in an aquatic insect Chironomus dilutus. Lethal and sublethal outcomes were assessed in the midges after 96-h exposure to imidacloprid. Global transcriptomic profiles were determined using de novo RNA-sequencing to more holistically identify toxicity pathways. Transcriptional 10% biological potency values derived from ranked KEGG pathways and GO terms were 0.02 (0.01-0.08) (mean (95% confidence interval) and 0.05 (0.04-0.06) µg L-1, respectively, which were more sensitive than those from phenotypic traits (10% lethal concentration: 0.44 (0.23-0.79) µg L-1; 10% burrowing behavior concentration: 0.30 (0.22-0.43) µg L-1). Major MoAs of imidacloprid in aquatic species were identified as follows: the activation of nicotinic acetylcholine receptors (nAChRs) induced by imidacloprid impaired organisms' nerve system through calcium ion homeostasis imbalance and mitochondrial dysfunction, which posed oxidative stress and DNA damage and eventually caused death of organisms. The current investigation highlighted that imidacloprid affected C. dilutus at environmentally relevant concentrations, and elucidated toxicity pathways derived from gene alteration to individual outcomes, calling for more attention to toxicity of neonicotinoids to aquatic organisms.

Spatiotemporal pattern analysis of schistosomiasis based on village level in the transmission control stage in lake and marshland areas in China.

Hubei Province is one of the endemic regions with severe schistosomiasis in China. To eliminate schistosomiasis in lake and marshland regions, this study detected hotspots of schistosomiasis cases both spatially and spatiotemporally on the basis of spatial autocorrelation; clustering and outlier, purely spatial and spatiotemporal cluster analyses at the village level from 2013 to 2017 in Hubei Province. The number of cases confirmed positive by an immunodiagnostic test and etiological diagnosis and advanced schistosomiasis cases dramatically declined during the study period. Significant global spatial autocorrelation of schistosomiasis patients was found at the village level in the whole province in 5 years. Clustering and outlier analysis showed that most HH villages were mainly concentrated along the Yangtze River, especially in Jianghan Plain. Spatial and spatiotemporal cluster analyses showed that significant clusters of the schistosomiasis cases were detected at the village level. In general, space and spatiotemporal clustering of schistosomiasis cases at the village level demonstrated a downward trend from 2013 from 2017 in Hubei Province. High-risk regions included Jianghan Plain along the middle reach of Yangtze River and Yangxin County in the lower reaches of the Yangtze River in Hubei Province. To eliminate schistosomiasis, precise control and management of schistosomiasis cases should be strictly implemented. Moreover, comprehensive prevention and control measures should be continuously strengthened in these regions.

The Predictive Value of Autoantibody Spectrum on Organ Damage in Patients With Systemic Lupus Erythematosus.

OBJECTIVES: This study aims to investigate the positive detection rate and predictive value of autoantibodies, including anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies, anti-histone antibodies (AHAs), anti-ribosomal (anti-Rib) P antibodies, anti-Smith (anti-Sm) antibodies, anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-Sjögren's syndrome type A antibodies and anti-Sjögren's syndrome type B antibodies, on organ damage in patients with systemic lupus erythematous (SLE). PATIENTS AND METHODS: A total of 225 patients with SLE (37 males, 188 females; mean age 37.4±15.9 years; range, 7 to 80 years) were evaluated retrospectively. Statistical analysis was performed to obtain the positive detection rate of autoantibodies and to investigate the predictive value. RESULTS: There were statistically significant differences of positive anti-dsDNA antibodies in renal damage, photosensitization, hematological abnormalities and serositis (p<0.05) and a statistically significant difference of positive AHAs in photosensitization (p<0.05). There was statistically significant difference of positive anti-U1RNP antibodies in renal damage (p<0.05). There were also statistically significant differences of positive anti-Smith antibodies in renal damage, arthritis, photosensitization, oral ulcers, hematological abnormalities and serositis (p<0.05) and of positive anti-Rib antibodies in renal damage, arthritis, photosensitization, malar rash, hematological abnormalities and serositis (p<0.05). However, there were no statistically significant differences of positive anti-Sjögren's syndrome type B antibodies and anti-Sjögren's syndrome type A antibodies in renal damage, arthritis, malar rash, neuropsychiatric disorders, hematological abnormalities and serositis (p>0.05). CONCLUSION: Autoantibody spectrum is an important serological basis for SLE diagnosis. There are differences in the autoantibodies distribution of SLE patients with different organ damage, suggesting a certain clinical value for prediction of organ damage in SLE.

Long non-coding RNA-OIS1 inhibits HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1.

Long non-coding RNA-oncogene-induced senescence 1 (lncRNA-OIS1) is a novel lncRNA that is involved in oncogene-induced senescence, while its functionality in cervical squamous cell carcinoma is unknown. In the present study, 68 human papillomavirus (HPV)-positive and 22 HPV-negative patients with cervical squamous cell carcinoma were recruited. Additionally, 40 healthy females were employed as healthy controls. Tumor tissues and adjacent healthy tissues were collected from all patients with cervical squamous cell carcinoma, and blood samples were obtained. Expression of OIS1 was detected by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of OIS1 for cervical squamous cell carcinoma. HPV-positive and HPV-negative cervical squamous cell carcinoma and normal cervical cell lines were used, and the effects of OIS1 or mitogen-activated protein kinase kinase kinase 4, (MTK-1) expression vector transfection on the proliferation of cell lines and MTK-1 expression were detected by CCK-8 assay and western blotting, respectively. It was established that a reduction in OIS1 expression level in tumor tissues was apparent only in HPV-positive patients. Serum levels of OIS1 were lower in HPV-positive patients compared with that in HPV-negative patients and healthy controls, and no significant differences were observed between HPV-negative patients and healthy controls. Serum levels of OIS1 were significantly associated with tumor size, but not distant tumor metastasis. OIS1 expression level was lower in HPV-positive cancer cell lines compared with that in HPV-negative cancer cell lines, while no significant differences were observed between HPV-positive and HPV-negative normal cell lines. OIS1 overexpression inhibited and MTK-1 overexpression promoted the proliferation of HPV-positive, but not HPV-negative cancer or normal cell lines. OIS1 transfection also decreased the expression of MTK-1 in HPV-positive cancer cell lines, but not in any of the other cell lines. Therefore, it was concluded that OIS1 inhibited HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1.

Long non-coding RNA UCA1 modulates the glycolysis of cervical cancer cells by miR-493-5p/HK2.

Long noncoding RNAs (lncRNAs) are associated with tumor development and progression. LncRNA UCA1 (UCA1) recently has been reported to take part in cancer cell proliferation. However, the expression and underlying molecular mechanism of UCA1 in cervical cancer cell glycolysis is unclear. This study aimed to investigate the role of UCA1 in cervical cancer. In order to explore the role of UCA1 in cervical cancer, first, the expression levels of UCA1 in cervical cancer tissues were measured, and the results showed that UCA1 levels were higher in cancer tissues compared to matched adjacent normal tissues. The inhibition of UCA1 expression suppressed human cervical cancer cell proliferation and glycolysis. Additionally, our experimental results indicated that UCA1 could directly bind to miR-493-5p and regulate miR-493-5p expression in an inverse manner. Namely, UCA1 could reverse the inhibitory effect of miR-493-5p on cervical cancer cells' proliferation and glycolysis. Moreover, we revealed that HK2 is a target gene of miR-493-5p through a Targetscan prediction. It was verified that miR-493-5p downregulated HK2 mRNA and protein levels using real time RT-PCR and Western blotting. In a summary, this study demonstrated that UCA1 functioned as an oncogene by UCA1/miR-493-5p/HK2 axis in cervical cancer.

[Preparation and Molluscicidal Effect of Chlorosalicylicamide Sustained-release Granules].

Objective: To prepare the 5% and 10% chlorosalicylicamide（quinoid-2', 5-dichloro-4'-nitrosalicylanilide from niclosamide） sustained-release granules （LDS-SRG） and evaluate their molluscicidal effect. Methods: The 5% and 10% LDS-SRG were prepared with screened carriers, surfactants, adhesives, defoamers and lubricants. Their bulk density, water content, repose angle, critical relative humidity, thermal stability and release rate were determined. Spraying method was used to test the molluscicidal effect of LDS-SRG at 1.6 g/m2. Meanwhile, 50% wettable powder of niclosamide ethanolamine salt (WPN) was applied as the positive control at 1.0 g/m2, and dechlorinated water was used as the blank control. The mortality of snails was calculated on days 3, 7 and 14 after administration. Results: The 5% and 10% LDS-SRG were red brown in color, showed good fluidity, and had bulk density of 0.655 g/ml and 0.594 g/ml, moisture content of 1.15% and 1.28%, repose angle of 39.8° and 39.7°, and critical relative humidity of 64.98% and 61.63%, respectively. Moreover, both showed good thermal stability. The release curve was stable for both 5% and 10% LDS-SRG during day 1 to day 9, and faster release for 5% LDS-SRG than for 10% LDS-SRG. The burst release occurred on days 10 and 15, and the steady release occurred from days 14 and 20 for 5% and 10% LDS-SRG respectively. The snail mortality on day 7 after 5% LDS-SRG 1.6 g/m2 administration and on day 14 after 10% LDS-SRG 1.6 g/m2 administration was both higher than 95%, and higher than that of the 50% WPN 1.0 g/m2 control (P<0.05). Conclusion: The 5% and 10% LDS-SRG show sustained-release potential and satisfactory molluscicidal effect by spraying, reaching the evaluation standard for molluscicidal agents.