Study on the Molecular Mechanisms of dlk1 Stimulated Lung Cancer Cell Proliferation

Background and objective The imprinted gene dlk1 has been recognized as a cancer related gene since it aberrantly expressed in a series of cancer tissues, but its role in lung cancer is still unknown. The aim of this study is to examine dlk1’s expression in non-small cell lung cancers (NSCLCs) and investigate the molecular mechanism by which dlk1 could accelerate the proliferation of the cells in lung cancer cell lines (H520). Methods The relative expression of dlk1 among 30 NSCLC specimens and their adjacent normal lung tissues were analyzed by RT-PCR. A cell model that stably expressed exogenous dlk1 was established following that the dlk1 gene was cloned into a eukaryotic expression vector and then transfected into the lung cancer cells H520. CCK8 analysis and colony forming assay were employed to investigate the effect of dlk1 on cell proliferation. The expression of CyclinB1 was detected by Western blot. Results dlk1 aberrantly expressed in 36.7% (11/30) of the tumor tissues of NSCLC compared with their adjacent cancer lung tissues. CCK8 analysis showed that overexpression of dlk1 could promote the proliferation of H520 cells (P < 0.05) and the results was further confirmed by colony forming assay. Western blot analysis found that over expression of dlk1 could up-regulate the expression of CyclinB1 (P < 0.05). Conclusion dlk1 aberrantly expressed in NSCLCs. The Overexpression of dlk1 could accelerate the proliferation of lung cancer cells H520 in vitro, probably through up-regulating the expression of cell cycle protein CyclinB1

One Case of Autopsy Pathological Analysis of Acute Pancreatitis Combined with Hemorrhage in Pericardial Cavity

Senile male, physically ft at usual, he died suddenly without any clinical symptoms. By autopsy dissection, it was found that large amount of bleeding was presented in pericardial cavity, the abdominal cavity and thoracic cavity had a small amount of hemorrhage, partial pancrea tissue had coagulation necrosis accompanied with infltration of neutrophile granulocyte and degeneration and necrosis of liver cell accompanied with acute or chronic inflammation cell infltration. Laboratory examination of the patient when he was alive suggested that liver function and coagulation function had obstacles, there was not any timely clinical process, and he died suddenly. Autopsy examination results suggested that acute pancreatitis caused a large quantity of bleeding in pericardial cavity, which led to cardiac tamponade and it cause acute circulation failure, which initiated cardiac arrest and then death. Coronary heart disease may exert certain facilitation effect in the death process. Patients with pancreatitis, especially the senile and pancreatitis patients with coronary artery disease, should be evaluated and prevented ahead of schedule, for those patients who had coma suddenly, it should be thought that it had possibility of combining with hemorrhage in the interior of pericardial cavity, the patient's doctor should try his or her best to reduce death rate

The Healthcare and Societal Costs of Familial Intellectual Disability

Most of the studies on the cost of intellectual disability are limited to a healthcare perspective or cohorts composed of individuals where the etiology of the condition is a mixture of genetic and non-genetic factors. When used in policy development, these can impact the decisions made on the optimal allocation of resources. In our study, we have developed a static microsimulation model to estimate the healthcare, societal, and lifetime cost of individuals with familial intellectual disability, an inheritable form of the condition, to families and government. The results from our modeling show that the societal costs outweighed the health costs (approximately 89.2% and 10.8%, respectively). The lifetime cost of familial intellectual disability is approximately AUD 7 million per person and AUD 10.8 million per household. The lifetime costs to families are second to those of the Australian Commonwealth government (AUD 4.2 million and AUD 9.3 million per household, respectively). These findings suggest that familial intellectual disability is a very expensive condition, representing a significant cost to families and government. Understanding the drivers of familial intellectual disability, especially societal, can assist us in the development of policies aimed at improving health outcomes and greater access to social care for affected individuals and their families

Negative pressure irrigation increases vegetable water productivity and nitrogen use efficiency by improving soil water and NO3–-N distributions

peer reviewedNegative pressure irrigation (NPI), which is a new subsurface irrigation technique, promotes vegetable yield, water productivity (WP), and nitrogen use efficiency (NUE). However, it is not clear how NPI improves vegetable growth, especially in terms of water supply characteristics and uniformities of soil water and nitrogen. In this study, a cucumber pot experiment that had 0 kPa (PW1), –5 kPa (PW2), –10 kPa (PW3), –15kPa (PW4), and traditional irrigation (PCK) treatments under nitrogen application (N1) and no application (N0) was conducted to reveal the water supply characteristics of NPI and its effect on vegetable growth. There are two main water supply characteristics: 1) automatically supplying irrigation water based on the consumption of soil water, and 2) keeping soil water content stable during the vegetable growth period. In addition, the relationship between vegetable growth and soil water and NO3–-N distribution uniformities throughout the soil profile was investigated by carrying out two tomato field experiments. The treatments of one tomato experiment were NPI with –5 kPa (F1W) and furrow irrigation (F1CK). We also carried out NPI with –5 kPa (F2W), furrow irrigation (F2CK), and drip irrigation (F2D) in another tomato experiment. The results showed that cumulative water application under N1 was higher than under N0 in the PW1, PW2, and PW3 treatments in the cucumber experiment. Volumetric soil water content under the NPI system was more stable during the vegetative growth period than under traditional irrigation. The NPI system also increased yields under appropriate pressures (–10–0 kPa) compared to the PCK treatment in the cucumber experiment. The NPI in the two tomato experiments reduced fertilizer inputs and irrigation compared to furrow irrigation and drip irrigation. However, the irrigation method had no significant influence on the tomato yield in the two tomato experiments. © 2021 Elsevier B.V

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The Relationship between IGF Pathway and Acquired Resistance to Tyrosine Kinase Inhibitors in Cancer Therapy

The tyrosine kinase signaling pathway is an important pathway for cell signal transduction, and is involved in regulating cell proliferation, cell cycle, apoptosis and other essential biological functions. Gene mutations involved in the tyrosine kinase signaling pathway often lead to the development of cancers. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) are well known receptor tyrosine kinases (RTKs), which belong to the ERBB family and have high mutation frequency in cancers. Tyrosine kinase inhibitors (TKI) targeting EGFR and HER2 have been widely used in the clinical treatment of lung and breast cancers. However, after a period of treatment, patients will inevitably develop resistance to TKI. The insulin-like growth factor (IGF) receptor family, like the ERBB receptor family, belongs to the receptor tyrosine kinase superfamily, which also conducts an important cell signal transduction function. There is an overlap between IGF signaling and EGFR signaling in biological functions and downstream signals. In this review, we summarize the current state of knowledge of how IGF signaling interacts with EGFR signaling can influence cell resistance to EGFR/HER2-TKI. We also summarize the current drugs designed for targeting IGF signaling pathways and their research progress, including clinical trials and preclinical studies. Altogether, we aimed to discuss the future therapeutic strategies and application prospects of IGF signaling pathway targeted therapy

Robotic Furnace System for Carbon Nanotube (CNT) Growth

Team photo and abstract of the final report of Project 02 of ME450 from the Winter 2009 semester. Archive is limited to an abstract due to ongoing R&D of this project.Carbon nanotubes hold much promise with regards to their potential application in various fields. However, due to the sensitive nature of the manufacturing process, efforts to produce a batch that has uniform height have proven difficult. The key variables of this process have been identified to be the temperature of the gas and its composition when encountering the growth substrates. The objective of this project is to develop an automated control system to minimize and compensate for deviations in the driving variables, thus ensuring even growth across the batch. It is also necessary to give the user control over the batch's growth. This is to be done by implementing a real-time, in-situ growth measurement device as well as an automated furnace system.John Hart (Mechanical Engineering, U of M)http://deepblue.lib.umich.edu/bitstream/2027.42/62171/2/ME450 Winter2009 Team Photo - Project 02 - Robotic Furnace System for Carbon Nanotube (CNT) Growth.JPGhttp://deepblue.lib.umich.edu/bitstream/2027.42/62171/1/ME450 Winter2009 Final Abstract - Project 02 - Robotic Furnace System for Carbon Nanotube (CNT) Growth.pd

Utility of dominant epitopes derived from cell-wall protein LppZ for immunodiagnostic of pulmonary tuberculosis

Abstract Background Serological antibodies tests for tuberculosis (TB) are widely used in developing countries. They appear to have some advantages- faster, simple and could be used for extrapulmonary TB. However, most of current commercial TB serological tests are failed to provide sufficient sensitivity and specificity. Improved serological biomarkers were essential. In this study, we present an approach using peptide array to discover new immunodiagnostic biomarkers based on immunodominant epitopes of TB antigens. Results The Probable conserved lipoprotein LppZ, which is difficult to express and purify in vivo was selected as the model antigen. We use two-step screening for dominant epitope selection. Based on peptide array data from 170 TB patients and 41 control samples, two dominant epitopes were identified to have diagnostic value for TB patients. Truncation assay was used to identify the core reactive sequence. Peptide- based ELISA was used to evaluate the diagnostic ability of pep-LppZ-1 and pep-LppZ-13. Pep-LppZ-1 has a sensitivity of 49.2% and a specificity of 83.3% in TB diagnose. Pep-LppZ-13 has a sensitivity of 43.3% and a specificity of 88.5% in TB diagnose. Conclusions Our result demonstrated that peptide array screening would be an advantage strategy of screening TB diagnostic peptides

Identification of serum MiRNAs as candidate biomarkers for non-small cell lung cancer diagnosis

Abstract Background Lung cancer is one of the most common solid tumors worldwide and the leading cause of cancer-associated death. Non-small cell lung cancer (NSCLC) is accounts for approximately 85% of all the lung cancers and lung squamous carcinoma (SCC) and adenocarcinoma (ADC) are the main subtypes of NSCLC. Early diagnose using serum biomarkers could improve the overall survival of patients. In this study, we aimed to identify miRNAs from serum with clinical utility in the diagnosis of NSCLC. Methods Ten patients with SCC, ten patients with ADC and five noncancerous individuals were enrolled in the screening cohort. miRNA expression levels in serum were measured by microarray analysis. Candidate miRNAs were validated by real-time quantitative polymerase chain reaction analysis in a validation cohort of 78 NSCLC patients and 44 noncancerous individuals. Receiver operating characteristic curves were used to assess the diagnostic performance of serum miRNAs for NSCLC. Logistic regression was used to evaluate the diagnostic value of the combination of markers. Results Six candidate miRNAs were differentially expressed between NSCLC patients and noncancerous individuals in the screening set (fold change > 2, p < 0.05). Among them, expression levels of miR-3149 and miR-4769.3p were confirmed to be significantly increased in tumor serum in the validation set. The area under the curve values of miR-3149 and miR-4769.3p in distinguishing NSCLC patients from noncancerous controls were 0.830 and 0.735, respectively. When combined with tumor markers CEA and Cyfra21-1, the joint diagnostic model increased the area under the curve to 0.898. Conclusion Serum miRNAs miR-3149 and miR-4769.3p were up-regulated in NSCLC and may be potential biomarkers for early diagnosis of lung cancer

Chiral Covalent Organic Frameworks with High Chemical Stability for Heterogeneous Asymmetric Catalysis

Covalent organic frameworks (COFs) featuring chirality, stability, and function are of both fundamental and practical interest, but are yet challenging to achieve. Here we reported the metal-directed synthesis of two chiral COFs (CCOFs) by imine-condensations of enantiopure 1,2-diaminocyclohexane with <i>C</i>₃-symmetric trisalicylaldehydes having one or zero 3-<i>tert</i>-butyl group. Powder X-ray diffraction and modeling studies, together with pore size distribution analysis demonstrate that the Zn­(salen)-based CCOFs possess a two-dimensional hexagonal grid network with AA stacking. Dramatic enhancement in the chemical stability toward acidic (1 M HCl) and basic (9 M NaOH) conditions was observed for the COF incorporated with <i>tert</i>-butyl groups on the pore walls compared to the nonalkylated analog. The Zn­(salen) modules in the CCOFs allow for installing multivariate metals into the frameworks by postsynthetic metal exchange. The exchanged CCOFs maintain high crystallinity and porosity and can serve as efficient and recyclable heterogeneous catalysts for asymmetric cyanation of aldehydes, Diels–Alder reaction, alkene epoxidation, epoxide ring-opening, and related sequential reactions with up to 97% ee