A binary pulsar in a 53-minute orbit.

Spider pulsars are neutron stars that have a companion star in a close orbit. The companion star sheds material to the neutron star, spinning it up to millisecond rotation periods, while the orbit shortens to hours. The companion is eventually ablated and destroyed by the pulsar wind and radiation1,2. Spider pulsars are key for studying the evolutionary link between accreting X-ray pulsars and isolated millisecond pulsars, pulsar irradiation effects and the birth of massive neutron stars3-6. Black widow pulsars in extremely compact orbits (as short as 62 minutes7) have companions with masses much smaller than 0.1 M⊙. They may have evolved from redback pulsars with companion masses of about 0.1-0.4 M⊙ and orbital periods of less than 1 day8. If this is true, then there should be a population of millisecond pulsars with moderate-mass companions and very short orbital periods9, but, hitherto, no such system was known. Here we report radio observations of the binary millisecond pulsar PSR J1953+1844 (M71E) that show it to have an orbital period of 53.3 minutes and a companion with a mass of around 0.07 M⊙. It is a faint X-ray source and located 2.5 arcminutes from the centre of the globular cluster M71.

[The epidemiological characteristics of pneumoconiosis in Qingyuan City from 1949 to 2018].

Objective: In order to find out the prevalence and death of pneumoconiosis in Qingyuan City, to explore the regularity of pneumoconiosis and lay a foundation for the prevention and management of pneumoconiosis. Methods: In August to December 2019, the basic data of pneumoconiosis from 1949 to 2018 were obtained through the monitoring of death causes of residents, occupational disease management system, Guangdong population information system and other means. The reported cases of pneumoconiosis were followed up, and retrospective investigation was conducted to analyze the basic conditions, the length of service exposed to dust, the time of diagnosis, the type of disease, the stage and the combined status of tuberculosis of pneumoconiosis cases. Results: From 1949 to 2018, a total of 466 cases of new pneumoconiosis were reported in Qingyuan City, including 325 cases of death (69.74%) , 114 cases of survival (24.46%) and 27 cases of loss of follow-up (5.80%) . The cases were mainly concentrated in the age group of 40-89 years (80.04%, 373/466) . There were 411 male cases (88.20%) and 7 female cases (1.50%) . The median length of service exposed to dust was 10.7 (6.0, 16.0) years. The diagnosis time of pneumoconiosis cases was mainly from 1949 to 1986 (68.67%, 320/466) , and the death cases were mainly from 1949 to 1986 (82.77%, 269/325) . Silicosis was the main type of pneumoconiosis (398 cases, 85.41%) . 200 cases (42.92%) were diagnosed as stage I pneumoconiosis, 185 cases (39.69%) were stage II pneumoconiosis, 81 cases (17.38%) were stage III pneumoconiosis at the first diagnosis. 102 cases (21.89%) were pneumoconiosis with tuberculosis. The proportion of death and lost follow-up cases diagnosed as stage I pneumoconiosis for the first time was significantly lower than that of survival cases, and the proportion diagnosed as stage II pneumoconiosis and the complication rate of tuberculosis were significantly higher than those of survival cases (χ(2)=15.48, 11.29, 32.73, P<0.001) . Conclusion: Pneumoconiosis in Qingyuan City is mainly silicosis. The number of new cases has been increasing in the past decade, and the prevention and control situation is still severe. The comprehensive prevention and treatment of silica dust should be included in the focus of supervision of government functional departments.

[Anatomical recognition of pancreatic membrane and its application in surgery].

With the rise of domestic membrane anatomy and preliminary establishment of theoretical framework, the operation concepts supported by membrane anatomy are gaining popularity in surgery, especially in abdominal surgery. However, on account of a deep location and the complexity of organs and tissues around the pancreas and mesangial membrane, there is no unified understanding about the pancreas mesangial by experts and scholars. Meanwhile, few studies on it have been conducted. In addition, the location and extent of total mesangectomy based on the mesangial pancreatic theory are also controversial. The purpose of this article is to summarize the anatomy of pancreatic membrane and its application in surgery, in order to provide support for current studies on pancreatic mesangial anatomy.

Efficacy and safety of fosaprepitant in the prevention of nausea and vomiting following highly emetogenic chemotherapy in Chinese people: A randomized, double-blind, phase III study.

The prevention of chemotherapy-induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2-d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0-120 hr, overall phase [OP]). It was assessed by using a non-inferiority model, with a non-inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi-square analysis. Six hundred and twenty-six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin-based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well-tolerated control of nausea and vomiting associated with HEC in Chinese patients.

Genetic analysis of QTL for eye cross and eye diameter in common carp (Cyprinus carpio L.) using microsatellites and SNPs.

A group of 107 F1 hybrid common carp was used to construct a linkage map using JoinMap 4.0. A total of 4877 microsatellite and single nucleotide polymorphism (SNP) markers isolated from a genomic library (978 microsatellite and 3899 SNP markers) were assigned to construct the genetic map, which comprised 50 linkage groups. The total length of the linkage map for the common carp was 4775.90 cM with an average distance between markers of 0.98 cM. Ten quantitative trait loci (QTL) were associated with eye diameter, corresponding to 10.5-57.2% of the total phenotypic variation. Twenty QTL were related to eye cross, contributing to 10.8-36.9% of the total phenotypic variation. Two QTL for eye diameter and four QTL for eye cross each accounted for more than 20% of the total phenotypic variation and were considered to be major QTL. One growth factor related to eye diameter was observed on LG10 of the common carp genome, and three growth factors related to eye cross were observed on LG10, LG35, and LG44 of the common carp genome. The significant positive relationship of eye cross and eye diameter with other commercial traits suggests that eye diameter and eye cross can be used to assist in indirect selection for many commercial traits, particularly body weight. Thus, the growth factor for eye cross may also contribute to the growth of body weight, implying that aggregate breeding could have multiple effects. These findings provide information for future genetic studies and breeding of common carp.

Overregulation of microRNA-212 in the poor prognosis of esophageal cancer patients.

There have been few reports evaluating the expression and function of the microRNA miR-212 in esophageal cancer. The aim of this study was to investigate the relationship between miR-212 expression and clinicopathological factors and prognoses of esophageal cancer. MicroRNA was extracted from 46 esophageal cancer patients using the Taqman MicroRNA assay. All patients were at the same tumor node metastasis stage, but with different prognoses, and had all undergone surgery. The correlation between miR-212 expression and clinicopathological features was analyzed and the significance of miR-212 as a prognostic factor as well as its relationship with survival was determined. miR-212 expression was higher in patients with poor prognoses than in those with good prognoses (P < 0.0001). Kaplan-Meier analysis results showed that the miR-212 expression level was significantly correlated with survival time (P = 0.024). Patients with higher expression of miR-212 showed longer survival times. Cox multi-factor model analysis showed that miR-212 expression was significantly correlated with survival time (P = 0.026). mir-212 is related with prognostic factors and survival time and may be a biomarker for esophageal cancer.

Mg composition dependent band offsets of Zn(1-x)Mg(x)O/ZnO heterojunctions.

The valence band offsets (ΔEV) of Zn(1-x)Mg(x)O/ZnO heterojunctions grown by plasma-assisted molecular beam epitaxy were measured by photoelectron spectroscopy. From the directly obtained ΔEV values, the related conduction band offsets (ΔEC) were deduced. All the Zn(1-x)Mg(x)O/ZnO heterojunctions exhibit a type-I band alignment with the ΔEC/ΔEV estimated to be 1.5, 1.8, 2.0 for x = 0.10, 0.15 and 0.20, respectively. The band offsets of Zn(1-x)Mg(x)O/ZnO heterojunctions depend on Mg composition. The accurate determination of energy band alignment of Zn(1-x)Mg(x)O/ZnO is helpful for designing ZnO based optoelectronic devices.

Electronic transport with dielectric confinement in degenerate InN nanowires.

In this Letter, we present the size effects on charge conduction in InN nanowires by comprehensive transport studies supported by theoretical analysis. A consistent model for highly degenerate narrow gap semiconductor nanowires is developed. In contrast to common knowledge of InN, there is no evidence of an enhanced surface conduction, however, high intrinsic doping exists. Furthermore, the room-temperature resistivity exhibits a strong increase when the lateral size becomes smaller than 80 nm and the temperature dependence changes from metallic to semiconductor-like. This effect is modeled by donor deactivation due to dielectric confinement, yielding a shift of the donor band to higher ionization energies as the size shrinks.

Tissue microarray assessment of selenoprotein P expression in gastric adenocarcinoma.

This study investigated selenoprotein P expression, using immunohistochemistry, in gastric adenocarcinoma tissue microarrays constructed from 30 gastric adenocarcinoma specimens and 30 normal gastric tissues (controls). Selenoprotein P expression scores were significantly lower in gastric adenocarcinoma (17/30, 56.7%) than in control tissues (25/30, 83.3%). Selenoprotein P was significantly more likely to be expressed in well-to-moderately differentiated cases (13/17, 76.5%) than in cases with low differentiation (4/13, 30.8%) and there was no significant difference in selenoprotein P expression between tumour node metastasis (TNM) stage I - II (11/19, 57.9%) and TNM stage III (6/11, 54.5%). In conclusion, selenoprotein P expression was low in gastric adenocarcinoma tissues compared with control tissues and was related to the degree of gastric adenocarcinoma differentiation but not to TNM stage.

Polymorphism of the PRNP gene in the main breeds of indigenous Chinese goats.

The polymorphism of the PRNP gene plays a key role in susceptibility to prion disease. Scrapie is a neurodegenerative disease affecting sheep and goats and belongs to the group of prion diseases. We isolated DNA from 333 goat samples representing the main local goat breeds in six provinces in China to identify PRNP polymorphisms and to determine whether these breeds were at risk for developing scrapie. Two novel amino acid polymorphisms (R211G and T219I) and a novel silent mutation at codon 125 as well as nine previously reported polymorphisms were observed. Twenty-eight alleles and forty-nine different genotypes were obtained. The codon 142M associated with resistance of goat scrapie was not found in this study. The codon 143R was relatively rare. The codon 222K, a potentially useful candidate site for selecting for scrapie resistance, was also rare in indigenous Chinese goats. These results could provide some useful data for assessing the risk of scrapie in Chinese indigenous goats.

Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-alpha-induced epithelial-mesenchymal transition of MCF-7 cells.

The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-alpha (TNF-alpha). To evaluate the role of TNF-alpha in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-alpha-treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-alpha treatment. These results showed that TNF-alpha can promote epithelial-mesenchymal transition (EMT) of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkappaB) inhibitor aspirin while not affected by the reactive oxygen species (ROS) scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkappaB by the mutant IkappaBalpha also blocked the TNF-alpha-induced upregulation of Snail promoter activity. Thus, the activation of NFkappaB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-alpha-induced EMT. ROS caused by TNF-alpha seemed to play a minor role in the TNF-alpha-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-alpha- and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

Role of nuclear factor kappa B and reactive oxygen species in the tumor necrosis factor-a-induced epithelial-mesenchymal transition of MCF-7 cells

The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-alpha (TNF-alpha). To evaluate the role of TNF-alpha in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-alpha-treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-alpha treatment. These results showed that TNF-alpha can promote epithelial-mesenchymal transition (EMT) of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB) inhibitor aspirin while not affected by the reactive oxygen species (ROS) scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBalpha also blocked the TNF-alpha-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-alpha-induced EMT. ROS caused by TNF-alpha seemed to play a minor role in the TNF-alpha-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-alpha - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.

[Synthesis, preliminary antigastrelcosis activity and the protective effect on acute liver injury of zinc chlorin E4].

AIM: To study the synthesis of zinc chlorin e4(1), its experimental antigastrelcosis activity as well as the protection against acute liver injuries. METHODS: Chlorin e6(3) was prepared through acidic and alkaline oxidative degradation using silkworm excrement crude chlorophyll extracts as starting material. Compound 1 was synthesized via Zn(OAc)2 complex action with Chlorin e4(2) which was prepared by refluxing 3 in pyridine. Gastric ulcers were induced by abdominal injection of 0.2% indomethacin at 20 mg.kg-1 in rats. The ulcer indexes and ulcer numbers in gastric mucosa were determined. Acute liver injuries were induced by abdominal injection of 0.3% thioacetamide (TAA) or 0.3% CCl4 at 20 mg.kg-1 in mice, and activities of SGPT in mice were determined. RESULTS: Compound 1 is previously unknown. Compared with control group, abdominal administration of 1 at 100 mg.kg-1 reduced significantly the gastric ulcer index (P < 0.001) and the number of ulcer (P < 0.001) induced by indomethacin in rats. Abdominal administration of 1 at 100 mg.kg-1 x 3 exhibited marked inhibitory effects on elevated activities of SGPT induced by TAA (P < 0.02) or CCl4(P < 0.01) in mice. CONCLUSION: These results show that 1 has significant protective effect against indomethacin-induced gastric lesion in rats and TAA or CCl4 induced acute liver injuries in mice. It is suggested that 1 may be a promising new drug candidate for antigastrelcosis and liver injury protection.

Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease.

Daclizumab, a humanized monoclonal IgG1 directed against the alpha chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%). Survival on day 120 was 29% (95% CI, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3( + )25(+) lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (Blood, 2000; 95:83-89)

Effective depletion of alloreactive lymphocytes from peripheral blood mononuclear cell preparations.

BACKGROUND: T cells present in an allogeneic bone marrow transplant may produce graft-versus-host disease but also contribute to immune reconstitution and enhance engraftment. Our aim was to separate alloreactive from nonalloreactive T lymphocytes, by performing a mixed lymphocyte culture (MLC) stimulation of donor cells, followed by selective depletion of activated cells expressing the high-affinity interleukin 2 receptor. We then characterized the resulting depleted cell fraction. METHODS: Donor peripheral blood mononuclear cells were cocultured with irradiated peripheral blood mononuclear cells from HLA-nonidentical recipient stimulators in an MLC. After 3 days, CD25+ lymphocytes (alloreactive cells expressing the alpha chain of the interleukin 2 receptor) were removed by immunomagnetic separation. The depleted donor fraction and untreated cells were then rechallenged in a secondary MLC with the original irradiated stimulator cells or a third party to assess relative alloreactivity. RESULTS: Inhibition of the secondary MLC and of host-specific cytotoxic activities was observed as well as a disappearance of interleukin 2 receptor-positive cells. Alloreactivity against unrelated third-party cells was preserved. Limiting dilution analysis of residual alloantigen-reactive T lymphocytes demonstrated a 1.3 log reduction of antihost reactivity. The depletion largely removed host-specific alloreactive CD4+ cells. CONCLUSIONS: This method reduces alloreactivity while retaining reactivity against third-party targets. This approach may allow therapeutic infusion of T cells after HLA-nonidentical allografts with a reduced capacity to produce graft-versus-host disease.

Debulking blood stem cell collections by density gradient centrifugation in a closed-vessel system.

BACKGROUND: Blood stem cells collected by apheresis are largely mononuclear cells in nature, so manipulation of blood stem-cell components frequently requires more time and reagents than for a marrow harvest. Reducing the nucleated cell number in mobilized blood stem-cell collections, while preserving hematopoietic progenitor content, would make such manipulations simpler and less costly, but only if debulking procedures were not complex. METHODS: We evaluated separation of light-density cells and enrichment of CD34+ cells from mobilized peripheral blood stem-cell collections by density gradient centrifugation over buoyant density solution 60 (BDS 60) in a single, closed vessel. RESULTS: Fifteen apheresis products from five normal volunteers and eight cancer patients contained 3.44 (range, 1.19-5.51) x 10(10) nucleated cells. Following processing and washing, there was a median 29% recovery of nucleated cells, 79% recovery of CD34+ cells, 2.49-fold enrichment of CD34+ cells, 0.96-log depletion of CD3+ cells, 0.48-log depletion of CD56+ cells, and 0.72-log depletion of CD19+ cells. Results of processing were affected by the variability in composition of the apheresis products. The enrichment of CD34+ cells varied by donor type, and there was a logarithmic relationship between the preprocessing percentage of CD19+ cells and the log reduction in CD19+ cells. Recovery of cells after thawing and washing was acceptable for processed cells cryopreserved at concentrations over the range of 0.01-1.5 x 10(8)/mL. DISCUSSION: These results demonstrate a simple method by which an apheresis product of 1-5 x 10(10) cells can be debulked effectively in a single, closed vessel.

[Comparative molecular field analysis (CoMFA) of allylamine antimycotics].

Active analog approach has been applied to determine the pharmacophoric conformations of the allylamine antimycotics. Comparative molecular field analysis (CoMFA) has been used to establish 3D-QSAR of 48 allylamine antimycotics against six common human pathogenic fungi. Two different alignment rules were compared in the meantime. Five new synthetic compounds have been successfully employed to examine the predictive abilities of the CoMFA models against Trichophyton mentagrophytes and Aspergillus fumigatus.

Inflammatory cytokine expression is correlated with the level of human immunodeficiency virus (HIV) transcripts in HIV-infected placental trophoblastic cells.

The inflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) have been associated with increased human immunodeficiency virus (HIV) expression and enhanced lymphocyte adhesion to trophoblastic cells in experimental systems. To determine if there is a correlation between the expression of these cytokines and the levels of HIV transcripts in trophoblasts of term placentas from HIV-infected women, we studied the placentae of 30 HIV-positive and 13 control gravidae. Twenty-three of the HIV-positive women received zidovudine (ZDV) as prophylaxis against HIV vertical transmission; only one of the seven women who did not receive ZDV was a transmitter, for an overall vertical transmission rate of 3.8%. Cytokine production was measured by enzyme-linked immunosorbent assay in the supernatants of trophoblastic cell cultures. Additionally, cytokine transcripts and HIV gag sequences were determined by a quantitative reverse transcription-PCR assay. In general, trophoblastic cells of HIV-positive placentas expressed significantly higher levels of IL-1beta, IL-6, and TNF-alpha than those of control placentas. All placentas from HIV-positive women expressed HIV gag transcripts at either a low (<156 copies per microg of total RNA) or a high (>156 copies per microg of total RNA) level. There was a statistically significant positive association between the basal level of TNF-alpha production and the level of HIV gag transcripts of HIV-positive placental trophoblastic cells. Nevertheless, these data, coupled with a low transmission rate, would indicate that some other factors, perhaps working in concert with cytokines, are necessary for vertical transmission of HIV from mother to infant.

Quantification of IL-2 and IL-2 receptor mRNA in peripheral blood mononuclear cells by the RT-PCR based SHARP Signal system.

Nuclear transcription assays have shown that increases in interleukin 2 (IL-2) and its receptor (IL-2R) mRNA are reflected at the level of transcription. However, the quantification of transient and low-level expression of IL-2/IL-2R mRNAs in normal resting peripheral blood mononuclear cells (PBMC) requires a sensitive and reliable assay. We have established a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) assay to measure IL-2/IL-2R transcripts by modifying the commercially-available SHARP Signal system to include IL-2/IL-2R RNA probes that were constructed by in vitro transcription of phagemid clones. To evaluate this modified SHARP Signal system and to demonstrate its clinical utility, the expression levels of IL-2 and IL-2R were assessed for 40 healthy normal donors. The mean +/- SEM levels of transcripts in normal PBMC expressed in zeptomol per micrograms total RNA for IL-2, IL-2R alpha and IL-2R beta were 2.6 +/- 0.5, 23.3 +/- 2.2 and 157.2 +/- 32.2 respectively. Compared with the conventional RT-PCR and gel-electrophoresis-based detection method, the SHARP Signal system is fast, not labor-intensive and inexpensive, and can be readily adapted for the measurement of other cytokines or cytokine receptor gene expressions in a clinical diagnostic laboratory environment without extensive experience in molecular techniques.

[Synthesis and antifungal activities of 1-(2-[(substituted-phenyl) methyl]thio)-2-(2,4-difluorophenyl)ethyl-1H-1,2,4-triazoles].

Twenty-one 1-[2-[[(substituted-phenyl) methyl] thio]-2-(2, 4-difluorophenyl) ethyl]-1H-1,2,4-triazoles were synthesized and 19 compounds are reported for the first time. Results of biological tests in vitro showed that the antifungal activities of all title compounds were better than or comparable to the activities of fluconazole. The antifungal activities of compounds 1-7 and 11-17 were better than or comparable to the activities of sulconazole. Compounds 1, 2 and 5 were 512 times more active than sulconazole against epidermophyton floccosum; compound 5 was 32 times more active against Candida albicans, compound 2 was 32 times more active against Sporotrichum schenckii; compounds 2 and 14 were shown to be 64 and 32 times more active against Cryptococcus neoformans; compounds 1 and 5 were 16 times more active against Aspergillus fumigatus.