TYK2 promotes malignant peripheral nerve sheath tumor progression through inhibition of cell death

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that arise most commonly in the setting of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome. Despite aggressive multimodality therapy, outcomes are dismal and most patients die within 5 years of diagnosis. Prior genomic studies in our laboratory identified tyrosine kinase 2 (TYK2) as a frequently mutated gene in MPNST. Herein, we explored the function of TYK2 in MPNST pathogenesis. METHODS: Immunohistochemistry was utilized to examine expression of TYK2 in MPNSTs and other sarcomas. To establish a role for TYK2 in MPNST pathogenesis, murine and human TYK2 knockdown and knockout cells were established using shRNA and CRISPR/Cas9 systems, respectively. RESULTS: We have demonstrated that TYK2 was highly expressed in the majority of human MPNSTs examined. Additionally, we demonstrated that knockdown of Tyk2/TYK2 in murine and human MPNST cells significantly increased cell death in vitro. These effects were accompanied by a decrease in the levels of activated Stats and Bcl-2 as well as an increase in the levels of Cleaved Caspase-3. In addition, Tyk2-KD cells demonstrated impaired growth in subcutaneous and metastasis models in vivo. CONCLUSION: Taken together, these data illustrate the importance of TYK2 in MPNST pathogenesis and suggest that the TYK2 pathway may be a potential therapeutic target for these deadly cancers

Role of District Education Officials in Quality Education in Nanguan and Shikarpur Districts: A Comparative Study Between China and Pakistan

The purpose of the study is to understand the role of district educational official(s) in bringing quality in education in schools at district level with respect to the educational objectives at ministry of education level, provincial education department level and at local district level. Two districts; Nanguan district (China) and Shikarpur district (Pakistan) are studied and compared with each other because of the convenience for researcher and good friendship between these two countries. This is comparative study, which adopts descriptive type of research, and qualitative research design. Semi-structured interview and observation report; are used as research tools for data collection. Purposive sampling type is adopted as to make this study possible to complete and having strong relationship of district educational officials’ interventions with quality in education in variety of schools. District educational official(s) and four schools (primary, junior secondary, countryside and city) in each district are visited. Results of the study show that district educational officials of both districts are aware about the educational objectives at these three levels of educational administration. They perceive quality in education differently with respect to their local and contextual environment. Arranging different trainings for school heads and teachers and calling meetings are the only two similar interventions among these two district educational officials that they take to achieve quality in education; rest interventions are totally different. There seems more implication of the interventions of the Nanguan district education bureau official in the schools than the implication of the interventions of Shikarpur district educational officials in schools; as to achieve their perceived quality in education in their respective districts

Experimental study on the isothermal adsorption of methane gas in natural gas hydrate argillaceous silt reservoir

Gas hydrate occurs in hydrate reservoirs in a solid form. At present, the conventional exploitation method is to decompose solid hydrate and then extract the resulting gaseous gas. Therefore, the occurrence law of gas in a reservoir is of great significance for the study of gas hydrate seepage and productivity. Adsorption, as an important occurrence mode, has been widely concerned in the research on shale reservoirs. However, the adsorption problem in hydrate reservoirs has not received enough attention. In this paper, the existence of adsorption in a hydrate reservoir has been experimentally confirmed for the first time. Based on the argillaceous silt of a natural gas hydrate reservoir in the South China Sea, the pore structure and adsorption characteristics of argillaceous silt were experimentally studied, and the results were compared with those of typical shale reservoirs. The modified Langmuir and Dubinin-Radushevich equations were used to fit the adsorption data, and the suitable adsorption model of argillaceous silt was established and optimized. The results showed that the inhomogeneous slit pores are dominant in argillaceous silt, and they are formed by the accumulation of lamellar particles. Compared with shale, the adsorption capacity of argillaceous silt is weak under the same conditions. However, adsorption is a spontaneous exothermic reaction, and the ambient temperature of argillaceous silt is much lower than that of shale. Therefore, it is possible for argillaceous silt to achieve an adsorption capacity comparable to that of shale. The modified Langmuir model can be used to simulate argillaceous silt adsorption at low pressure, while under medium and high pressures, the modified Dubinin-Radushevich model performs better. The adsorption capacity of argillaceous silt is affected by moisture. When the water content is 20%, the Langmuir adsorption capacity and the Dubinin-Radushevich maximum adsorption capacity decreases by 21.88% and 13.67%, respectively, which is far less than the influence of moisture on shale adsorption, as reported in the literature.Cited as: Qi, R., Qin, X., Lu, C., Ma, C., Mao, W., Zhang, W. Experimental study on the isothermal adsorption of methane gas in natural gas hydrate argillaceous silt reservoir. Advances in Geo-Energy Research, 2022, 6(2): 143-156. https://doi.org/10.46690/ager.2022.02.0

Long Non-Coding RNA TUG1 Attenuates Insulin Resistance in Mice with Gestational Diabetes Mellitus via Regulation of the MicroRNA-328-3p/SREBP-2/ERK Axis

Background Long non-coding RNAs (lncRNAs) have been illustrated to contribute to the development of gestational diabetes mellitus (GDM). In the present study, we aimed to elucidate how lncRNA taurine upregulated gene 1 (TUG1) influences insulin resistance (IR) in a high-fat diet (HFD)-induced mouse model of GDM. Methods We initially developed a mouse model of HFD-induced GDM, from which islet tissues were collected for RNA and protein extraction. Interactions among lncRNA TUG1/microRNA (miR)-328-3p/sterol regulatory element binding protein 2 (SREBP-2) were assessed by dual-luciferase reporter assay. Fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA pancreatic β-cell function (HOMA-β), insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and insulinogenic index (IGI) levels in mouse serum were measured through conducting gain- and loss-of-function experiments. Results Abundant expression of miR-328 and deficient expression of lncRNA TUG1 and SREBP-2 were characterized in the islet tissues of mice with HFD-induced GDM. LncRNA TUG1 competitively bound to miR-328-3p, which specifically targeted SREBP-2. Either depletion of miR-328-3p or restoration of lncRNA TUG1 and SREBP-2 reduced the FBG, FINS, HOMA-β, and HOMA-IR levels while increasing ISOGTT and IGI levels, promoting the expression of the extracellular signal-regulated kinase (ERK) signaling pathway-related genes, and inhibiting apoptosis of islet cells in GDM mice. Upregulation miR-328-3p reversed the alleviative effects of SREBP-2 and lncRNA TUG1 on IR. Conclusion Our study provides evidence that the lncRNA TUG1 may prevent IR following GDM through competitively binding to miR-328-3p and promoting the SREBP-2-mediated ERK signaling pathway inactivation

Study on different potato continuous cropping ways on rhizosphere soil nutrients and enzyme activities

To address the problem of food security, China produced potatoes as a staple food in 2015.However, there are increasing problems with continuous cropping production methods, potato continuous cropping has been inevitable.So it is necessary to research under the different potato continuous cropping ways, potato rhizosphere soil nutrients and enzyme activities which can direct potato fertilizer and ease potato continuous cropping obstacle. A two-growing season investigation was carried out during the spring and autumn of 2014 and 2015 to determine the different ways of potato continuous cropping on the overall growth of potatoes, soil nutrients, and enzyme activities. During continuous cropping nitrogen (N) content of rhizosphere soil was reduced; available potassium (Kav) was significantly reduced(p≤5%), especially in spring and autumn continuous cropping; and total phosphorus (Ptot) was reduced during the growth stage. However, the total potassium (Ktot), available phosphorus(Pav), and organic carbon (Ctot) increased before they decreased. For rhizosphere soil enzyme activities, urease initially increased and then decreased, and was lower in continuous cropping than multiple continuous cropping; in spring of 2015, invertase was the highest with continuous cropping. Catalase and polyphenol oxidase decreased initially before increasing. Continuous cropping in spring and autumn consumed more nutrients, especially potassium (K) than in spring. Therefore, potatoes planted in both spring and autumn enhanced the problems of continuous cropping. However, multiple continuous cropping that eased rhizosphere soil nutrient absorption and effectively improves soil nutrients and enzyme activities could provide an effective method for managing the negative impacts associated with continuous cropping

Bacterial Communities in the Womb During Healthy Pregnancy

The idea that healthy uterine cavity is sterile is challenged nowadays. It is still debatable whether the bacteria present in the uterine cavity during pregnancy are residents or invaders. To reveal microbiome composition and its characteristics in the womb of pregnant women, 41 decidual tissue samples and 64 amniotic fluid samples were taken from pregnant Chinese women. DNA extraction was followed by pyrosequencing of the hypervariable V4 region of the 16S rDNA gene to characterize womb microbiome. Both types of samples had low diversity microbiome with Enterobacteriaceae being the dominant phylotypes at family level. To characterize the nature of colonization during pregnancy, the presence of endogenous biomass was confirmed by cultivation. Surprisingly, all of the 50 amniotic fluid samples studied were culture-negative, whereas 379 out of 1,832 placenta samples were culture-positive. Our results suggested that womb contained microbiome with low diversity. Culture-based investigation of amniotic fluid and placenta samples confirmed the presence of cultivable microorganisms in the placenta but not in amniotic fluid. Thus it suggests that bacterial colonization does occur during healthy pregnancy

Clinical characteristics and lateralization of the horizontal semicircular canal light cupula

IntroductionPositional vertigo and nystagmus are the main symptoms and signs of dizziness, respectively. Despite the clinical utility of the supine roll test (SRT) and null point (NP) in diagnosing light cupula, a type of positional vertigo, there exists a notable gap in the literature concerning the comprehensive evaluation of lateralization values based on various nystagmus characteristics and the intensity of direction-changing positional nystagmus (DCPN) in the SRT, particularly in comparison to the NP. Additionally, limited data on abnormal canal paresis (CP) in light cupula patients underscores the need for further research with a larger patient population to elucidate this mechanism. This study aims to investigate the characteristics of positional nystagmus and lateralization of the horizontal semicircular canal (HSCC) light cupula, which is a type of positional vertigo and nystagmus that is poorly understood.MethodsEighty-five patients (17 males, 68 females; mean age, 60.9 years) with light cupula were reviewed. We summarized the characteristics of spontaneous nystagmus and positional nystagmus, including supine positioning nystagmus, bow nystagmus, and lean nystagmus. Then, the side of the NP was identified as the affected side, and the values of the fast phase direction of the spontaneous nystagmus, supine positioning nystagmus, bow nystagmus, and lean nystagmus, as well as the intensity of the DCPN in the SRT, were used to diagnose the affected sides. Caloric testing was also performed for some patients.ResultsLight cupula was observed in 5.7% of the patients with positional nystagmus. The frequencies of supine positioning nystagmus (88.2%), bow nystagmus (90.6%), and lean nystagmus (83.5%) were higher than spontaneous nystagmus (61.2%) (p < 0.001). The second NP (NP2) (92.9%) and third NP (NP3) (83.5%) were readily detected, affecting the left and right sides in 38 and 47 patients, respectively. Lateralization through the fast phase directions of bow nystagmus and lean nystagmus did not significantly differ from that of NP (all p > 0.05). However, the accuracy rate of lateralization through the sides with more vigorous DCPN in the SRT was 63.5%, significantly lower than through NP (p < 0.001). Particularly in patients with supine positioning nystagmus (n = 75), the rate was only 58.7% (p < 0.001). However, the rate was 100% in patients without supine positioning nystagmus (n = 10). Among the 70 patients who underwent caloric testing, 37 had abnormal CP, and the sides of the reduced caloric reaction were ipsilateral to the affected sides of the light cupula in 83.8% of the patients.ConclusionBesides utilizing the NP to determine the affected side, the fast phase direction of the bow nystagmus or lean nystagmus can also aid in identification. However, a simple comparison of the intensity of DCPN in SRT cannot provide accurate lateralization, especially in patients with supine positioning nystagmus. There is a high incidence of CP on the affected side of the light cupula

Crystal plane engineering of MAPbI3 in epoxy-based materials for superior gamma-ray shielding performance

The rapid development of the aerospace and nuclear industries is accompanied by increased exposure to high-energy ionising radiation. Thus, the performance of radiation shielding materials needs to be improved to extend the service life of detectors and ensure the safety of personnel. The development of novel lightweight materials with high electron density has therefore become urgent to alleviate radiation risks. In this work, new MAPbI3/epoxy (CH3NH3PbI3/epoxy) composites were prepared via a crystal plane engineering strategy. These composites delivered excellent radiation shielding performance against 59.5 keV gamma rays. A high linear attenuation coefficient (1.887 cm−1) and mass attenuation coefficient (1.352 cm2 g−1) were achieved for a representative MAPbI3/epoxy composite, which was 10 times higher than that of the epoxy. Theoretical calculations indicate that the electron density of MAPbI3/epoxy composites significantly increases when the content ratio of the (110) plane in MAPbI3 increases. As a result, the chances of collision between the incident gamma rays and electrons in the MAPbI3/epoxy composites were enhanced. The present work provides a novel strategy for designing and developing high-efficiency radiation shielding materials

Gender-specific association between the regular use of statins and the risk of irritable bowel syndrome: A population-based prospective cohort study

Introduction: In addition to lipid-lowering effects, statins might modulate the gut microbiome and alleviate systematic inflammation, which in turn, may have a protective effect against irritable bowel syndrome (IBS). The aim of our study was to evaluate the gender-specific association between statin exposure and the risk of IBS.Method: We undertook a prospective analysis based on the United Kingdom Biobank, a large ongoing cohort including 477,293 participants aged 37–73 years. We included participants based on information on their personal statin use and also those free of IBS and cancer at the baseline. We evaluated the gender-specific hazard ratio (HR) and 95% confidence interval (CI) with Cox proportional hazards regression, adjusting for demographic factors, lifestyle factors, comorbidities, and statin indications.Result: A total of 438,805 participants (206,499 males and 232,306 females) were included in the analysis. Among male participants, the regular use of statins was associated with a decreased risk of IBS (HR: 0.77; 95% CI: 0.61–0.97). This association persists across multiple sensitivity and subgroup analyses and did not show clear evidence of variance among the major types of statins. We did not find sufficient evidence of the association between the statin use and IBS risk in females (HR: 0.98; 95% CI: 0.82–1.16).Conclusion: Our study found that the regular use of statins was associated with a decreased risk of IBS in male participants. Further studies are required to confirm the beneficial effect of statins