Spatial distribution of NH2D in massive star-forming regions

To understand the relation between NH$_2$D and its physical environment, we mapped ortho-NH$_2$D $1_{11}^s-1_{01}^a$ at 85.9 GHz toward 24 Galactic late-stage massive star-forming regions with Institut de Radioastronomie Millim$\'e$trique (IRAM) 30-m telescope. Ortho-NH$_2$D $1_{11}^s-1_{01}^a$ was detected in 18 of 24 sources. Comparing with the distribution of H$^{13}$CN 1-0 as a dense gas tracer and radio recombination line H42$\alpha$, ortho-NH$_2$D $1_{11}^s-1_{01}^a$ present complex and diverse spatial distribution in these targets. 11 of the 18 targets, present a different distribution between ortho-NH$_2$D $1_{11}^s-1_{01}^a$ and H$^{13}$CN 1-0, while no significant difference between these two lines can be found in the other 7 sources, mainly due to limited spatial resolution and sensitivity. Moreover, with H42$\alpha$ tracing massive young stellar objects, ortho-NH$_2$D $1_{11}^s-1_{01}^a$ seems to show a relatively weak emission near the massive young stellar objects.Comment: 30 pages, 20 figures, 4 tables. Accepted to MNRA

Distribution of Spectral Lags in Gamma Ray Bursts

Using the data acquired in the Time To Spill (TTS) mode for long gamma-ray bursts (GRBs) collected by the Burst and Transient Source Experiment on board the Compton Gamma Ray Observatory (BATSE/CGRO), we have carefully measured spectral lags in time between the low (25-55 keV) and high (110-320 keV) energy bands of individual pulses contained in 64 multi-peak GRBs. We find that the temporal lead by higher-energy gamma-ray photons (i.e., positive lags) is the norm in this selected sample set of long GRBs. While relatively few in number, some pulses of several long GRBs do show negative lags. This distribution of spectral lags in long GRBs is in contrast to that in short GRBs. This apparent difference poses challenges and constraints on the physical mechanism(s) of producing long and short GRBs. The relation between the pulse peak count rates and the spectral lags is also examined. Observationally, there seems to be no clear evidence for systematic spectral lag-luminosity connection for pulses within a given long GRB.Comment: 20 pages, 4 figure

Colorectal cancer screening with fecal occult blood test: A 22-year cohort study.

The aim of the present study was to investigate the efficacy of colorectal cancer (CRC) screening with a three-tier fecal occult blood test (FOBT) in the Chinese population. The study was performed between 1987 and 2008 at the Beijing Military General Hospital, in a cohort of army service males and females aged >50 years. Between 1987 and 2005, a three-tier screening program, comprising guaiac-based FOBTs (gFOBTs), followed by immunochemical FOBTs for positive guaiac test samples and then colonoscopy for positive immunochemical test subjects, was performed annually. The cohort was followed up until 2008. The cohort included 5,104 subjects, of which, 3,863 subjects participated in screening (screening group) and 1,241 did not (non-screening group). The two groups did not differ in age, gender or other major risk factors for colon cancer. Overall, 36 CRCs occurred in the screening group and 21 in the non-screening group. Compared with the non-screening group, the relative risk for the incidence and mortality of CRC was 0.51 [95% confidence interval (CI), 0.30-0.87] and 0.36 (95% CI, 0.18-0.71), respectively, in the screening group. The general sensitivity of this three-tier FOBT was 80.6% (95% CI, 65.3-91.1). Thus, annual screening using the three-tier FOBT program may reduce the CRC incidence and mortality rate

Phase-resolved spectral analysis of 4U 1901+03 during its outburst

The high mass X-ray binary 4U 1901+03 was reported to have the pulse profile evolving with the X-ray luminosity and energy during its outburst in February-July 2003: the pulse peak changed from double to single along with the decreasing luminosity. We have carried out a detailed analysis on the contemporary phase-resolved energy spectrum of 4U 1901+03 as observed by Rossi X-ray Timing Explorer (RXTE). We find that, both the continuum and the pulse spectra are phase dependent. The optical depth derived from the pulse spectrum is in general larger than that from the continuum. Fe Ka emission line is only detected in the spectrum of the continuum and is missing in the pulse spectrum. This suggests an origin of Fe emission from the accretion disk but not the surface of the neutron star.Comment: 18 pages, 8 figures, accepted by Ap

ESTROGEN ANCHORED NANOMICELLES FOR COMBINATIONAL DRUG DELIVERY WITH ENHANCED THERAPEUTIC EFFICACY: A PROTEOMICS GUIDED INVESTIGATION FOR MULTIFUNCTIONAL NANOTHERAPEUTICS

The employment of the stable isotope labeling with amino acids in cell culture (SILAC) based proteomic analysis as a guidance tool for investigation of cellular response of a multifunctional nanodelivery system has been described for cancer therapy. The multifunctional nanodelivery system in this study was based on an estrogen anchored multimodal nanomicelle (NPG). The key components of the multifunctional nanomicelle consist: β-cyclodextrin conjugated estrone (CDE1), an escort molecule; polymeric BH3 mimetic, a proapoptotic BcL-2 inhibitor; and the mitotic catastrophe agent paclitaxel. They were assembled into the nanomicelle by multiple weak interactions including hydrophobic/hydrophilic interaction and host-guest recognition. The resulting nanomicelle exhibited unimodal morphology with average size of 170 nm with sustained release. It was found that the nanoparticle exhibits excellent anti-tumor activities for the treatment of breast adenocarcinoma with exceptional targeting efficacy both in MCF-7 tumor bearing mice. NPG as a new drug delivery system demonstrated several merits such as the increased drug uptake in breast tumor tissue, low toxicity, potent tumor growth retardation and metastasis inhibition, as well as potential clinical practicality without compromising liver, kidney and immune function and ameliorating the conventional chemotherapeutics induced phlebitis in breast tumor bearing nude mice model. The systematic SILAC based proteomics study and the subsequent validation revealed that the synergistic induction of mitotic catastrophe through enhanced G2/M phase arrest and PI3K/Akt/mTOR mediated autophagy, account for the exceedingly potent anti-tumor activity of this convergent nanomicelle. Additionally, the verification of the top upregulated gene from the proteomics profiling revealed that the overexpression of zinc finger protein 350 (ZNF350/ZBRK1) is associated with the enhanced antitumor effect induced by NPG.KEYWORDS:  Drug targeting, Estrogen Receptor, Proteomics, Paclitaxel, Gossypol, SynergismÂ

Spatiotemporal Genotype Replacement of H5N8 Avian Influenza Viruses Contributed to H5N1 Emergence in 2021/2022 Panzootic

Since 2020, clade 2.3.4.4b highly pathogenic avian influenza H5N8 and H5N1 viruses have swept through continents, posing serious threats to the world. Through comprehensive analyses of epidemiological, genetic, and bird migration data, we found that the dominant genotype replacement of the H5N8 viruses in 2020 contributed to the H5N1 outbreak in the 2021/2022 wave. The 2020 outbreak of the H5N8 G1 genotype instead of the G0 genotype produced reassortment opportunities and led to the emergence of a new H5N1 virus with G1's HA and MP genes. Despite extensive reassortments in the 2021/2022 wave, the H5N1 virus retained the HA and MP genes, causing a significant outbreak in Europe and North America. Furtherly, through the wild bird migration flyways investigation, we found that the temporal-spatial coincidence between the outbreak of the H5N8 G1 virus and the bird autumn migration may have expanded the H5 viral spread, which may be one of the main drivers of the emergence of the 2020-2022 H5 panzootic.IMPORTANCESince 2020, highly pathogenic avian influenza (HPAI) H5 subtype variants of clade 2.3.4.4b have spread across continents, posing unprecedented threats globally. However, the factors promoting the genesis and spread of H5 HPAI viruses remain unclear. Here, we found that the spatiotemporal genotype replacement of H5N8 HPAI viruses contributed to the emergence of the H5N1 variant that caused the 2021/2022 panzootic, and the viral evolution in poultry of Egypt and surrounding area and autumn bird migration from the Russia-Kazakhstan region to Europe are important drivers of the emergence of the 2020-2022 H5 panzootic. These findings provide important targets for early warning and could help control the current and future HPAI epidemics.</p

Comparison of endocrine therapy and chemotherapy as different systemic treatment modes for metastatic luminal HER2-negative breast cancer patients —A retrospective study

PurposeThe purpose of this study was to evaluate endocrine therapy and chemotherapy for first-line, maintenance, and second-line treatment of hormone receptor-positive HER-2-negative metastatic breast cancer (HR+HER-2-MBC) and the relationship between different treatment options and survival.Patients and methodsThe patients included in this study were all diagnosed with metastatic breast cancer (MBC) at Shandong Cancer Hospital from January 2013 to June 2017. Of the 951 patients with MBC, 307 patients with HR+HER-2-MBC were included in the analysis. The progression-free survival (PFS) and overall survival (OS) of the various treatment modes were evaluated using Kaplan–Meier analysis and the log-rank test. Because of the imbalance in data, we used the synthetic minority oversampling technique (SMOTE) algorithm to oversample the data to increase the balanced amount of data.ResultsThis retrospective study included 307 patients with HR+HER-2-MBC; 246 patients (80.13%) and 61 patients (19.87%) were treated with first-line chemotherapy and first-line endocrine therapy, respectively. First-line endocrine therapy was better than first-line chemotherapy in terms of PFS and OS. After adjusting for known prognostic factors, patients receiving first-line chemotherapy had poorer PFS and OS outcomes than patients receiving first-line endocrine therapy. In terms of maintenance treatment, the endocrine therapy-endocrine therapy maintenance mode achieved the best prognosis, followed by the chemotherapy-endocrine therapy maintenance mode and chemotherapy-chemotherapy maintenance mode, and the no-maintenance mode has resulted in the worst prognosis. In terms of first-line/second-line treatment, the endocrine therapy/endocrine therapy mode achieved the best prognosis, while the chemotherapy/chemotherapy mode resulted in the worst prognosis. The chemotherapy/endocrine therapy mode achieved a better prognosis than the endocrine therapy/chemotherapy mode. There were no significant differences in the KI-67 index (&lt;15%/15-30%/≥30%) among the patients receiving first-line treatment modes, maintenance treatment modes, and first-line/second-line treatment modes. There was no statistical evidence in this study to support that the KI-67 index affected survival. However, in the first-line/second-line model, after SMOTE, we could see that KI-67 ≥ 30% had a poor prognosis.ConclusionsDifferent treatment modes for HR+HER-2-MBC were analyzed. Endocrine therapy achieved better PFS and OS outcomes than chemotherapy. Endocrine therapy should be the first choice for first-line, maintenance, and second-line treatment of HR+HER-2-MBC

Protection Effect of Exogenous Fibroblast Growth Factor 21 on the Kidney Injury in Vascular Calcification Rats

Background: Chronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats. Methods: The male Sprague-Dawley rats were divided into three groups: (1) control group, (2) Vitamin D3 plus nicotine (VDN)-induced VC group, (3) FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases (ALPs) activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of β-Klotho and FGF receptor 1 (FGFR1) protein were measured by enzyme-linked immunosorbent assay (ELISA). The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining. Results: The renal function impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% (34.750 ± 4.334 μmol/L vs. 27.630 ± 2.387 μmol/L) and 4.0% (7.038 ± 0.590 mmol/L vs. 6.763 ± 0.374 mmol/L; P \u3c 0.01), respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% (P \u3c 0.01) and 11.7% (P \u3c 0.05) as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. ELISA assays showed that the expression of β-Klotho, a component of FGF21 receptor system, was increased in VDN-treated VC rats by 37.4% (6.588 ± 0.957 pg/mg vs. 9.054 ± 0.963 pg/mg; P \u3c 0.01), indicating an FGF21-resistant state. Moreover, FGF21 treatment downregulated the level of β-Klotho in renal tissue by 16.7% (9.054 ± 0.963 pg/mg vs. 7.544 ± 1.362 pg/mg; P \u3c 0.05). However, the level of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21 administration (0.191 ± 0.0376 ng/mg vs. 0.189 ± 0.032 ng/mg vs. 0.181 ± 0.034 ng/mg; P \u3e 0.05). Conclusions: In the present study, FGF21 was observed to ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential therapeutic factor in CKD by cutting off the vicious circle between VC and kidney injury