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 expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells].

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and ß-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

No pulsed radio emission during a bursting phase of a Galactic magnetar.

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

[Expression of FATS in non-small cell lung cancer and its relationship with prognosis].

Objective: To investigate the expression of fragile-site associated tumor suppressor (FATS) in non-small cell lung cancer and its relationship with clinicopathological features and prognosis. Methods: A total of 140 non-small cell lung cancer (NSCLC) cases and 30 adjacent normal tissues were used to detect the expression level of FATS protein, and to analyze the relationship of FATS protein expression and clinicopathological features and prognosis of NSCLC. Results: Western blot showed that the expression of FATS in adjacent normal tissues was significantly higher than that in non-small cell lung cancer tissues. The results of immunohistochemistry showed that the high expression rate of FATS in 140 cases of NSCLC was 40.0%, and the high expression rate of FATS in 30 cases of adjacent tissues was 73.3%. The difference was statistically significant (P=0.01). Further analysis showed that the TNM stage (P=0.044) and lymph node metastasis (P=0.022) were significant difference between FATS high expression group and low expression group. The 6-year overall survival (OS) rates of NSCLC patients with FATS high-expression and low-expression were 57.1% and 23.8%, respectively, and the 6-year disease-free survival (DFS) rates were 53.6% and 21.4%, respectively, with statistically significant differences (P=0.001). In Cox multivariate analysis, we found gender (HR=1.658, P=0.028; HR=1.684, P=0.023), TNM staging (HR=2.327, P=0.019; HR=2.332, P=0.013) and FATS expression (HR=0.532, P=0.010; HR=0.538, P=0.009) were independent prognostic factors for both OS and DFS of NSCLC patients. Conclusions: The expression of FATS protein is associated with the development and is an independent prognostic factor of NSCLC patients. The detection of FATS protein is expected to be a new biomarker for evaluating the prognosis of NSCLC patients.

Ultra-low radiation dose CT angiography of the lower extremity using the iterative model reconstruction (IMR) algorithm.

AIM: To investigate the image quality of lower-extremity computed tomography (CT) angiography (CTA) with ultra-low radiation dose using the iterative model reconstruction (IMR) algorithm. MATERIALS AND METHODS: Lower-extremity CTA was acquired using a 256-multidetector CT system from 90 patients assigned into three groups: (1) the routine dose (RD) group: 120 kVp, automatic tube current modulation (ACTM) with an image quality index of 12, and filtered back projection (FBP); (2) the low-dose (LD) group: 80 kVp, ACTM with an image quality index of 1, and IMR; and (3) the ultra-low dose (ULD) group: 80 kVp, 20 mAs, and IMR. CT attenuation, image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the lower-extremity arteries were calculated. Subjective image quality of lower-extremity segments was assessed. Effective radiation dose was recorded. RESULTS: The radiation dose was reduced by 91.4% and 67.3% in the ULD group (0.15±0.02 mSv) compared to the RD group (1.86±0.51 mSv) and the LD group (0.49±0.08 mSv; both p<0.05). Higher CT attenuation, SNR, CNR, and lower image noise were obtained in the ULD group and the LD group compared to the RD group (all p<0.05). Better subjective image quality in lower leg segments was obtained in the ULD group and the LD group compared to the RD group (all p<0.05). No difference was found between the ULD and LD groups in both objective and subjective image quality (all p>0.05). CONCLUSION: By using IMR during lower-extremity CTA, the radiation dose is reduced by up to 91.4% without compromising image quality.

Incidence, etiology, management, and outcomes of flank hernia: review of published data.

PURPOSE: To review the published data describing the incidence, etiology, management, and outcomes of flank hernia. METHODS: A retrospective review of articles identified with an online search (using the terms "flank hernia", "flank bulge", "lateral hernia", "retroperitoneal aorta hernia", and "open radical nephrectomy") was performed. Studies exclusively on lumbar hernia or subcostal hernia were excluded. RESULTS: All articles retained for analysis (N = 26) were uncontrolled series or case reports; there were no controlled trials. The incidence of incisional hernia in the flank was ~ 17% (total patients analyzed = 1,061). Flank hernia repair was accomplished successfully with a variety of techniques, with overall mean rates of perioperative complications, chronic post-procedure pain, and recurrence equal to 20, 11, and 7%, respectively. Mesh utilization was universal. CONCLUSIONS: The available data of outcomes of flank hernia repair are not of high quality, and recommendations essentially consist of expert opinions. Operative approach (open vs. laparoscopic) and mesh insertion details have varied, but reasonable results appear possible with a number of techniques.

Effects of oleic acid on SP-B expression and release in A549 cells.

OBJECTIVE: Pulmonary surfactant-associated protein B (SP-B), which is synthesized and secreted by alveolar epithelial type II cells, is crucial for normal functioning of pulmonary surfactant. Degeneration of pulmonary surfactant is the essential cause of acute lung injury (ALI). ALI is often studied in animal models using oleic acid, and the effects of oleic acid on pulmonary surfactant and SP-B are not clear. In this study, we examined the effects of oleic acid on the A549 cell line which resembles the alveolar epithelial type II cells. MATERIALS AND METHODS: A549 cells were exposed for 24 hours to 300, 400, 500 or 600 µM of oleic acid. Cell morphological changes were observed using an inverted microscope, and cell proliferation was quantified with the Cell Counting Kit-8. Extracellular SP-B levels were assessed by ELISA, whereas intracellular SP-B expression by Western blot. RESULTS: Oleic acid caused dose-dependent changes in cell morphology of A549 cells and decreased their proliferation. This was accompanied by release of SP-B into extracellular supernatants and corresponding decrease of intracellular levels of this protein. CONCLUSIONS: Oleic acid causes a dose-dependent injury to A549 cells, release of SP-B into extracellular compartment, and decrease of intracellular SP-B expression. Our findings provide mechanistic insights into animal modeling of ALI with oleic acid.

[Transcriptional regulation of the human gene coding for proline-rich nuclear receptor coactivator (pnrc) by regulatory factor x (rfx1)].

PNRC (Proline-rich Nuclear Receptor Coactivator) is a novel coactivator for multiple nuclear receptors. PNRC was previously identified using bovine SF-1 (steroidogenic factor 1) as the bait in a yeast two-hybrid screening of a human mammary gland cDNA expression library. To understand the molecular mechanisms that regulate the expression of human PNRC gene, in this study, functional analysis of the 5' flanking region of the human PNRC gene revealed that the -123/+27 region is the minimal promoter of the human PNRC gene. Gel shift and ChIP analyses demonstrated the specific binding of RFX1 (Regulatory Factor X) protein to the human PNRC promoter region. In co-transfection experiments RFX1 was shown to repress promoter activity of PNRC gene in a dose-dependent manner. These results indicate that r RFX1 specifically bind to promoter region and negatively regulate the transcription of the human PNRC gene.

Molecular epidemiologic analysis of group A rotaviruses in adults and children with diarrhea in Wuhan city, China, 2000-2006.

To compare epidemiologic features and genetic characteristics of group A rotaviruses causing diarrhea in children and adults, a survey was conducted in Wuhan, China, during the period of Dec. 2000-May 2006. A total of 3839 stool specimens from diarrheal patients from eight hospitals were analyzed. Winter seasonality was observed for rotavirus diarrhea in both adults and children, showing overall rotavirus-positive rates of 9.0 and 23.9%, respectively. Throughout the study period, G3 was the most frequent G serotype in both adults and children (detection rates 86.2 and 87.8%, respectively), and was mostly associated with VP4 genotype P[8], VP 6 genotype II (subgroup II), and NSP4 genotype B. G3 rotaviruses were differentiated into eight electropherotypes, among which seven types were found in specimens from both adults and children. VP7 gene sequences of G3 rotaviruses from adults and children (6 and 4 strains, respectively), detected in different years and different hospitals, showed extremely high sequence identities (99-100%) to each other and to a few G3 rotavirus strains reported in Asia. However, lower sequence identities (82-96%) were observed to most of the human and animal G3 rotaviruses reported so far, including some Chinese strains. These findings indicate that in Wuhan, China, epidemic and genetic features of rotaviruses are similar in adults and children, and it has been suggested that G3 rotaviruses that might have originated from the same rotavirus were circulating among children and adults as prevailing viruses. In this study, two rotavirus strains, G9P[8] strain L169, derived from an adult, and G4P[6] strain R479, derived from a child, were isolated and genetically analyzed. The VP7 gene of L169 belongs to a major lineage of G9 rotaviruses that are globally widespread, but is distinct from G9 rotaviruses reported previously in China. The strain R479 had a VP7 gene which was divergent from most G4 human rotaviruses and showed an unusual dual subgroup specificity, I + II. The R479 VP6 gene does not belong to the main clusters of subgroup I and II rotaviruses phylogenetically, but is related to those of the porcine rotaviruses and some unusual human rotaviruses represented by the RMC321 strain isolated in eastern India.

A site-directed mutagenesis study of human placental aromatase.

Aromatase, a cytochrome P-450, catalyzes the formation of aromatic C18 estrogenic steroids from C19 androgens. Using the x-ray structure of cytochrome P-450cam as the model, seven mutants of human aromatase were designed and expressed in Chinese hamster ovary cells by a stable expression method. They are His-128----Gln, His-128----Ala, Cys-299----Ala, Glu-302----Leu, Asp-309----Asn, Asp-309----Ala, and Ser-312----Cys. The presence of the aromatase mutants in the transfected Chinese hamster ovary cells were confirmed by immunoprecipitation analysis. The kinetic parameters of these mutants using [1 beta,2 beta-3H] androstenedione (or [1 beta-3H]androstenedione), and [1 beta,2 beta-3H]testosterone as substrates were determined. In addition, inhibition profiles for these mutants with two aromatase inhibitors, 4-hydroxyandrostenedione and aminoglutethimide were obtained. Furthermore, the reactions catalyzed by these mutants were examined by evaluating the levels of the product estrone, and two intermediates, 19-hydroxyandrostenedione and 19-oxoandrostenedione by reverse phase high performance liquid chromatography using [7-3H]androstenedione as the substrate. Our results indicate that among the positions we modified, Asp-309 appears to be very important for the enzyme catalysis.

[Changes in leucocytic estrogen receptor levels in patients with climacteric syndrome and therapeutic effect of liuwei dihuang pills].

The numbers of estrogen receptor (ER) in human peripheral leucocytes in 22 women with climacteric syndrome were measured by radioligand method. The results were compared with those of 12 normal child-bearing-age women. It wat found that the contents of leucocytic ER in climacteric syndrome patients were significantly lower than normal child-bearing-age women. The authors used a Chinese prescription--Liuwei Dihuang Pills (LDP) to treat the patients for 2 months. The numbers of leucocytic ER were significantly increased after treatment. The data indicate that decrease of ER levels in cell may involve in the pathogenesis of climacteric syndrome. LDP not only increases plasma estradiol levels, but also increases the leucocytic ER levels. This may be the basis of the therapeutic effect on the disease.

[Changes in levels of leucocytic estrogen receptor in patients with menopausal type II diabetes and its significance].

The number of estrogen receptors (ER) in human peripheral leucocytes in 12 women with menopausal type II diabetes was measured with radio-ligand binding method. The results were compared with those of 12 menopausal women without diabetes and 12 normal women of childbearing age. It was found that the number of ER in the patients was significantly decreased. Our data indicate that decrease of ER level in leukocytes may be related to the pathogenesis of type II diabetes in menopausal period.

[Changes in leucocytic estrogen receptor levels in patients with gynecomastia].

The number of estrogen receptor (ER) in human peripheral leucocytes in 13 men with gynecomastia were measured by radioligand binding method. The results were compared with those of 13 sex-and age-matched healthy subjects. It was found that the number of ER in leucocytes was significantly increased in gynecomastia (Rs of leucocytes were 1054 +/- 254 sites/cell). It suggested that increase of ER levels play an important role in the pathogenesis of gynecomastia.

Structure-function studies of human aromatase by site-directed mutagenesis: kinetic properties of mutants Pro-308----Phe, Tyr-361----Phe, Tyr-361----Leu, and Phe-406----Arg.

Aromatase, a cytochrome P450, catalyzes the formation of aromatic C-18 estrogenic steroids from C-19 androgens. Four mutants of human aromatase have been expressed in Chinese hamster ovary cells using a stable expression method. The activities of these mutants were determined using [1 beta,2 beta-3H]androstenedione, [19-14C]androstenedione, and [1 beta,2 beta-3H]testosterone as substrates. The mutant Phe-406----Arg was completely inactive. Since there were only small changes in the Km and Vmax values for all substrates for mutants Tyr-361----Phe and Tyr-361----Leu, the residue Tyr-361 appears not to be directly involved in the substrate binding. The mutant Pro-308----Phe had altered catalytic properties; the Km values for androstenedione, but not testosterone, decreased significantly. These results, along with those obtained from inhibition studies with aromatase inhibitors, 4-hydroxyandrostenedione and aminoglutethimide, suggest that Pro-308 is probably situated in the active site of the enzyme and may be interacting with the D ring of the steroids.

Stable expression of human aromatase complementary DNA in mammalian cells: a useful system for aromatase inhibitor screening.

A mammalian cell expression plasmid, pH beta-Aro, containing the human placenta aromatase complementary DNA was constructed. The prepared plasmid was used to transfect breast cancer cells (MCF-7), noncancerous breast cells (HBL-100), and Chinese hamster ovary cells by a stable expression method. While the maximum velocities for aromatase expressed in three types of cells were different (10-201 pmol of [3H2O] formed/h/mg) using [1 beta, 2 beta-3H]androst-4-ene-3,17-dione as the substrate, the apparent Michaelis-Menten constants were found to be similar (39.9-57.8 nM) and were within the range determined for the enzyme existing in human placenta. The expressed activities were inhibited by the known aromatase inhibitors, 4-hydroxyandrostenedione and aminoglutethimide, at concentrations that normally inhibit the human placental aromatase. However, it was found that the inhibition profiles were different for aromatase expressed in different types of cells, suggesting that other factors, such as the uptake of the inhibitor, may also play a role in determining the inhibition efficiency. These constructed aromatase expressing mammalian cell lines will be very useful tools for aromatase inhibitor screening.