Note: Calibration of majority isotopes for enriched and depleted uranium fission chambers by using the elimination method with fast neutrons.

Calibrated miniature pulse fission chambers (MPFCs) can be used for absolute measurement of the fission reaction rate in neutronic experiments. Absolute measurements require the effective number of fissionable atoms (ENFAs) in the coating of the chambers. An elimination method was proposed to calibrate the MPFCs embodying highly enriched and depleted uranium, using 14.75 MeV fast neutrons from the D-T reaction. The ENFAs of 235U in enriched uranium MPFC and 238U in depleted uranium MPFC are 8.39 × 1018 and 9.55 × 1018, with the uncertainties of 5.27% and 4.76%, respectively.

[The effect of human islet amyloid polypeptide on autophagy in murine INS-1 cells and potential mechanisms].

Objective: The aims of the study were to investigate the effects of human islet amyloid polypeptide (hIAPP) on autophagy in INS-1 cells and its underlying mechanism, and to explore the role of autophagy in hIAPP-induced cytotoxicity and oxidative stress. Methods: INS-1 cells were treated with hIAPP (10 µmol/L) for 24 h in the presence or absence of N-acetyl-L-cysteine (NAC), compound C, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) and 3-methyladenine (3-MA), respectively. Transmission electron microscopy was used to observe the number of autophagosome in cells. Cell viability was determined by methyl thiazolyl tetrazolium (MTT) test. 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to measure the relative levels of reactive oxygen species (ROS). Western blot was used to detect expression of adenosine monophosphate-activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain3 (LC3). Results: Treatment of INS-1 cells with hIAPP resulted in a significant increase in the number of autophagosomes and the expression of LC3-Ⅱ/LC3-Ⅰ (both P<0.05). Meanwhile, treatment of INS-1 cells with hIAPP enhanced the level of ROS to 1.76 times of control cells (P<0.01). Co-treatment with NAC, an antioxidant, inhibited hIAPP-induced ROS generation, and the expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK in the INS-1 cells (all P<0.05). Pretreatment of INS-1 cells with AMPK inhibitor compound C suppressed hIAPP and AICAR, an activator of AMPK, induced expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK (all P<0.05). Autophagic inhibitor 3-MA and compound C aggravated the hIAPP-induced cell death and ROS generation in INS-1 cells (All P<0.05). The cytotoxic effects of hIAPP were significantly attenuated by co-treatment with AICAR (P<0.05). Conclusion: Autophagy may act as an adaptive mechanism to alleviate hIAPP-induced oxidative damage and toxicity in INS-1 cells.

Epithelial barrier dysfunctions in atopic dermatitis: a skin-gut-lung model linking microbiome alteration and immune dysregulation.

BACKGROUND: Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. OBJECTIVES: This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. METHODS: A literature search was conducted using the PubMed database for relevant articles with the keywords 'atopic dermatitis', 'epithelial barrier', 'skin', 'gut', 'lung', 'microbiome' and 'immune dysregulation'. RESULTS: Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin-mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract. CONCLUSIONS: As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long-term outcomes and reduce allergen sensitization in the airway and gut.

[Role and clinical significance of coagulation and inflammatory factors in moderate and severe ovarian endometriosis].

Objective: To determine the levels of coagulation and inflammatory factors in women with moderate and severe ovarian endometriosis so as to investigate the possible role of coagulation and inflammatory factors in the pathogenesis, diagnosis and treatment of this disease. Methods: From June 2015 and June 2017, clinical data of 366 patients with pathologically diagnosed moderate and severe ovarian endometriosis (case group) and 244 patients with pathologically diagnosed benign ovarian cysts (control group) in Women's Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The levels of coagulation indicators, inflammatory factors and serum tumor markers were measured. Then, the values of these indicators in diagnosis of endometriosis were analyzed. Results: (1) The levels of plasma prothrombin time (PT) and thrombin time (TT) in patients with ovarian endometriosis [median: 12.8 s (range: 12.4-13.2 s) and 15.5 s (range: 15.1-15.9 s), respectively] were significantly shorter than those with benign ovarian cysts [median: 13.0 s (range: 12.5-13.4 s) and 15.7 s (range: 15.3-16.1 s), respectively; allP<0.01]. The levels of plasma fibrinogen (FIB) and D-dimer [D-D; median: 3.1 g/L (range: 2.8-3.5 g/L) and 0.9 mg/L (range: 0.6-2.1 mg/L) , respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.8 g/L (range: 2.6-3.2 g/L) and 0.6 mg/L (range: 0.4-1.2 mg/L), respectively; P=0.000]. Moreover, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio [PLR; median: 2.3 (range: 1.8-3.1) and 144 (range: 113-179), respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.1 (range: 1.6-2.8) and 128 (range: 104-165), respectively; P<0.01]. Furthermore, in patients with ovarian endometriosis, the levels of PT were significantly shorter in stage Ⅳ endometriosis than that in stage Ⅲ endometriosis (P<0.05). The levels of FIB and PLR in patients with stage Ⅳ endometriosis were significantly higher than those in patients with stage Ⅲ endometriosis (P<0.01) . (2) The cut-off value of CA(125) was 27.2 kU/L with a sensitivity of 83.6%, the cut-off value of FIB was 3.1 g/L with a sensitivity of 53.2%, while the sensitivity of combination index (FIB×CA(125)) was 84.9%. Conclusion: The abnormality of coagulation and inflammatory factors may be involved in the pathogenesis of moderate and severe ovarian endometriosis, and the detection of coagulation and inflammatory factors may be have important clinical significance for the diagnosis and treatment of moderate and severe ovarian endometriosis.

[A clinical analysis of 123 cases of primary empty sella].

Objective: This study was conducted to analyze the clinical characteristics and pituitary function of patients with primary empty sella (PES). Methods: The clinical data from 123 hospitalized adult patients with PES from January 2010 to May 2016 were retrospectively studied. Results: (1) The average age of the 123 (male 43, female 80) PES patients was (59.2±13.6) years (ranging 24-92 years), among whom 61% patients were in the age group between 50-69 years. (2) The symptoms of the patients included fatigue (56.1%), headache (34.1%), nausea and vomiting (17.9%), gonadal dysfunction (17.1%), visual disturbance (5.7%) and hypopituitarism crisis (3.3%). (3) Hypopituitarism was found in 66 of the 123 patients. Among them, 36.6%, 31.7% and 17.1% were central hypoadrenalism, hypogonadism, and hypothyroidism, respectively.The percentage of hypopituitarism in complete PES was significantly higher than that in partial PES (P<0.05). (4) Sixteen patients were concomitant with other autoimmune diseases including 11 patients with Graves' disease and 2 with Cushing's syndrome due to adrenal adenoma. Conclusions: The incidence of hypopituitarism in PES was 53.7%, in which the pituitary-adrenal axis hypofunction was more common. An overall evaluation of the pituitary function was essential for the patients who had headache and fatigue, or with suspected PES. The patients with hypopituitarism should be given hormone replacement therapy in time and followed up afterword.

[Correlation between polymorphism of angiotensin-converting enzyme gene and the lower extremity atherosclerosis in type 2 diabetes mellitus patients].

Objective: To explore the correlation between polymorphism of the angiotensin-converting enzyme (ACE) gene and lower extremity atherosclerosis (LEA) in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 380 patients diagnosed with T2DM in Department of Endocrinology from June 2015 to March 2016 were enrolled and divided into two groups: group A had no LEA (n=120) and group B had LEA(n=260). Color doppler ultrasound was used to detect the vascular lesions of the patients. For all patients in groups A and B, the polymerase chain reaction (PCR) was applied to determined the insertion/deletion polymorphism in intron 16 of the ACE gene of the patients. Then the blood pressure, blood lipid, glycated hemoglobin, and renal function were measured. Furthermore, the measured data was compared between the two groups. Multivariate logistic regression analysis was used to analyze the independent risk factors for LEA. Results: There was no significant statistical difference in age, sex, smoking and disease course between the two groups. The frequencies of DD genotype and D allele in the ACE gene of group B were much higher than those in group A. More specifically, DD genotype frequency was 18.8% in group B and 9.2% in group A, D allele frequency was 36.8% in group B and 29.2% in group A (all P<0.05). Multivariate logistic regression analysis showed that DD genotype in ACE gene (OR=2.744, 95% CI: 1.326-5.682), systolic blood pressure (OR=1.725, 95% CI: 1.072-2.778), total cholesterol (OR=3.785, 95% CI: 1.796-7.978), and glycated hemoglobin (OR=2.612, 95% CI: 1.602-4.258) were risk factors for LEA in T2DM patients. Conclusions: ACE gene insertion/deletion polymorphism was associated with the incidence of LEA in T2DM patients. DD genotype of the ACE gene may be a genetic risk factor for T2DM patients with concurrent atherosclerosis.

The impact of PASI 75 and PASI 90 on quality of life in moderate to severe psoriasis patients.

BACKGROUND: It is well known that psoriasis significantly impacts patients' quality of life (QoL). With the introduction of improved treatment modalities with biologic agents, more patients with moderate to severe psoriasis are able to achieve better results as measured by the Psoriasis Area and Severity Index (PASI). PASI 75 indicates a 75% or greater reduction in PASI scores from baseline and is indicative of excellent disease improvement. With newer biologic agents such as secukinumab, ixekizumab and brodalumab, patients are now capable of achieving PASI 90, introducing additional clinical decisions for physicians when considering treatment options. However, little is known regarding how the difference between achieving PASI-75 versus PASI-90 impacts patients' QoL. OBJECTIVES: The purpose of this study was to compare how achieving PASI 75 versus PASI 90 impacts QoL for patients with moderate to severe plaque psoriasis by using validated psychometric instruments that have been widely used in both dermatologic and non-dermatologic settings. METHODS: Two separate open-label clinical trials were conducted to specifically assess QoL in patients with moderate to severe psoriasis on adalimumab or ustekinumab over 24 weeks. In addition to clinical assessments of psoriasis, patients completed two surveys: The Psychological General Well-Being (PGWB) Index and the Dermatology Life Quality Index (DLQI). Changes in total PGWB score and DLQI score at weeks 12 and 24 compared to baseline were compared between groups achieving PASI 75 and PASI 90. RESULTS: There was no statistically significant difference in PGWB scores between patients achieving PASI 75 and patients achieving PASI 90 in the adalimumab treatment group (week 12 p = .21, but there was at week 24 p = .05). There was a statistically significant difference in DLQI between the patients achieving PASI 75 and the patients achieving PASI 90 in the adalimumab treatment group at week 24 (p = .01), but not week 12 (p = .11). There was no statistically significant difference in PGWB scores between patients achieving PASI 75 and patients achieving PASI 90 in the ustekinumab treatment group (week 12 p = .11, week 24 p = .35). There was no statistically significant difference in DLQI between the patients achieving PASI 75 and the patients achieving PASI 90 in the ustekinumab treatment group at week 24 (week 12 p = .49, week 24 p = .11). CONCLUSIONS: There has been tremendous attention surrounding newer biologic agents that can achieve PASI 90 and even PASI 100. Although the results are impressive with regard to physical improvement of psoriasis, there may not be a clinically significant difference in QoL when comparing patients who achieve PASI-75 versus PASI 90.

Molecular characterization, expression analysis and RNAi knock-down of elongation factor 1α and 1γ from Nilaparvata lugens and its yeast-like symbiont.

In the present paper, four cDNAs encoding the alpha and gamma subunits of elongation factor 1 (EF-1) were cloned and sequenced from Nilaparvata lugens, named NlEF-1α, NlEF-1γ, and its yeast-like symbiont (YLS), named YsEF-1α and YsEF-1γ, respectively. Comparisons with sequences from other species indicated a greater conservation for EF-1α than for EF-1γ. NlEF-1α has two identical copies. The deduced amino acid sequence homology of NlEF-1α and NlEF-1γ is 96 and 64%, respectively, compared with Homalodisca vitripennis and Locusta migratoria. The deduced amino acid sequence homology of YsEF-1α and YsEF-1γ is 96 and 74%, respectively, compared with Metarhizium anisopliae and Ophiocordyceps sinensis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the expression level of NlEF-1α and NlEF-1γ mRNA in hemolymph, ovary, fat body and salivary glands were higher than the midgut and leg tissue. YsEF-1α and YsEF-1γ was highly expressed in fat body. The expression level of NlEF-1α was higher than that of NlEF-1γ. Through RNA interference (RNAi) of the two genes, the mortality of nymph reached 92.2% at the 11th day after treatment and the ovarian development was severely hindered. The RT-qPCR analysis verified the correlation between mortality, sterility and the down-regulation of the target genes. The expression and synthesis of vitellogenin (Vg) protein in insects injected with NlEF-1α and NlEF-1γ double-stranded RNA (dsRNA) was significantly lower than control groups. Attempts to knockdown the YsEF-1 genes in the YLS was unsuccessful. However, the phenotype of N. lugens injected with YsEF-1α dsRNA was the same as that injected with NlEF-1α dsRNA, possibly due to the high similarity (up to 71.9%) in the nucleotide sequences between NlEF-1α and YsEF-1α. We demonstrated that partial silencing of NlEF-1α and NlEF-1γ genes caused lethal and sterility effect on N. lugens. NlEF-1γ shares low identity with that of other insects and therefore it could be a potential target for RNAi-based pest management.

First Report of Fusarium solani Causing Root Rot of Juglans sigllata Dode in China.

Juglans sigllata Dode, known as the iron walnut, is widely planted in Liangshan prefecture of southwest China for its nuts and wood. Liangshan prefecture is a major traditional growing area of J. sigllata and has unique advantages for walnut industrial development because of its good soil, climate, and availability of water. Currently there are 2.7 million hectares of walnut, contributing important incomes for farmers. In April 2013, numerous J. sigllata were found infected with root rot in the Muli county of Liangshan prefecture. Symptoms included dried leaves, dead branchcs, and even death. Rotted roots were collected and surface-sterilized in 2% NaOCl and 70% ethanol. The junction (1 cm) between infected and healthy regions was removed, plated on rose bengal-glycerin-urea medium, and incubated at 20°C for 12 h. A fungus was found and purified successively by transferring hyphal tips from the margin of a thinly growing colony on 2% water agar (3). Morphological characteristics were identified both on potato dextrose agar (PDA) and carnation leaf-piece agar. Evaluation of pigmentation and colony growth rate were also measured using PDA. Ovoid microconidia (average dimensions 10.6 × 9.1 µm) were observed after 2 to 3 days, and most of them had no septa or only one septum. Macroconidia (average dimensions 47.4 × 5.3 µm), with one to three septate sickle shapes, were found after 3 to 6 days. Single or paired chlamydospores (average dimensions 10.3 × 9.2 µm), which were circular to ovate, smooth or not smooth, were observed after 7 days of incubation in clean water. According to the cultural characteristics, the fungus was primarily identified as Fusarium solani (1). To better determine the species, universal primers ITS1/ITS4 for the ribosomal internal transcribed spacer (ITS) coupled with translation elongation factor (EF-1α) primers EF1/EF2 were used for PCR-based molecular identification. Against GenBank and the FUSARIUM-ID databases, our sequences shared 99 and 98% identities with ITS (FJ459973.1) and EF-1α (JX677562.1) of F. solani, respectively. Both sequences produced in this study have been deposited in GenBank under accession numbers KJ528277 for ITS and KJ528278 for EF-1α. Pathogenicity tests were conducted by drop inoculating 20 ml of microconidia suspension (106 spores/ml) on the roots of 1-year-old healthy potted J.sigllata, Mianyang walnut, and Xinjiang walnut. Controls were not treated with F. solani. Fifteen plants were in each group. All materials, including pots and soil, were disinfected. After 12 days, all J. sigllata inoculated with F. solani exhibited dried leaves, and after 17 days, Mianyang walnut and Xinjiang walnut infected with F. solani also developed the same symptoms. After 24 days, the inoculated J. sigllata died. However, control plants remained asymptomatic. The fungus re-isolated from infected roots showed the same characteristics as described above and was totally identical in appearance to the isolates used to inoculate the plants. No colonies of F. solani were isolated from untreated plants. At present, F. solani has been reported in stem cankers on English walnut in South Africa (2). To our knowledge, this is the first report of root rot caused by F. solani in J. sigllata in China. References: (1) C. Booth. Fusarium Laboratory Guide to the Identification of the Major Species. CMI, Kew, England, 1977. (2) W. Chen and W. J. Swart. Plant Dis. 84:592, 2000. (3) J. F. Leslie and B. A. Summerell. The Fusarium Laboratory Manual. Blackwell Publishing, Ames, IA, 2006.

A single ancestral gene of the human LIM domain oncogene family LMO in Drosophila: characterization of the Drosophila Dlmo gene.

Members of the human TTG/RBTN family, now renamed 'LMO' for LIM-only proteins, encode proteins with two tandem copies of a LIM motif. There are three members of this family, two have been isolated at the sites of chromosomal translocations in T-cell leukaemia. The function of the LIM motifs is at present unknown. We found that the LMO-2 gene is highly conserved between mammals, Drosophila and yeast. As a first step to obtain a model system for studying the function of the LIM motifs we have isolated the Drosophila homologue Dlmo. In contrast to mammals Drosophila appears to have only one lmo gene. A 2087 bp cDNA clone was isolated from a larval cDNA library, encoding a protein of 266 amino acids. A second transcript with an alternative 5' end was identified in RNA from embryos. The Drosophila lmo protein consists of two tandem copies of the conserved LIM domain characteristic of the human LMO family and an extended amino and carboxy terminus, which is not present in the human proteins. The amino acid sequence similarity with human LMO-1 and LMO-2 in LIM 1 is 79% and 69% and in LIM-2 90% and 60%, respectively. In addition a short stretch of 25 nucleotides with a homology of 83% between LMO-2 and Dlmo is found in the 3' UTR. Dlmo, like LMO-1, has an intron after the second LIM encoding region, which is not present in LMO-2. It is expressed maternally and at a high level in early embryogenesis as well as in adults. Interestingly we observed that the Dlmo protein is immunologically related to LMO-2 and can be detected by immunohistochemistry in early cellular blastoderm embryos. The gene was localised to a genetically well characterized region (17C on the X chromosome) opening the way for identification of mutations.

The TTG-2/RBTN2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p13 translocations in acute T cell leukaemia's (T-ALL).

The TTG-2 gene has been identified at the site of chromosomal translocations in acute T-cell leukemia's (T-ALL). These breakpoints map to a region between 2 and 30 kb upstream of TTG-2 in chromosome 11p13. To establish the role of these translocation breakpoints in the deregulation of TTG-2 in T-ALL we have determined the complete structure of this gene. Isolation of new TTG-2 cDNA clones from fetal liver identified an alternative transcript (TTG-2a) containing two new noncoding 5' exons. Analysis of exon/intron boundaries, identified 6 exons spread over 35 kb in 11p13. The gene encodes two alternative transcripts initiating from two promoters. TTG-2a, from promoter 1 (P1) and TTG-2b, from promoter 2 (P2) differ in the length of the 5' untranslated region, but encode the same protein. A high level of TTG-2a was present in fetal liver and spleen, whereas in adult kidney a low level of TTG-2a and a high level of TTG-2b was found. The transcription start site for TTG-2a was identified by RNase protection experiments and it displayed sequence homology to an initiator element (inr). P1 lacks a TATA box, but binding sites for SP1 and GATA-1 are present. This new genomic organisation revealed that all known chromosomal translocations map upstream of P2, removing P1 and putative upstream regulatory sequences leaving P2 intact. These results show that chromosomal translocations disrupt the TTG-2 gene itself, further confirming its role in the development of T-ALL.