Comparing human activity density and green space supply using the Baidu Heat Map in Zhengzhou, China

Rapidly growing cities often struggle with insufficient green space, although information on when and where more green space is needed can be difficult to collect. Big data on the density of individuals in cities collected from mobile phones can estimate the usage intensity of urban green space. Taking Zhengzhou\u27s central city as an example, we combine the real-time human movement data provided by the Baidu Heat Map, which indicates the density of mobile phones, with vector overlays of different kinds of green space. We used the geographically weighted regression (GWR) method to estimate differentials in green space usage between weekdays and weekends, utilizing the location and the density of the aggregation of people with powered-up mobile phones. Compared with weekends, the aggregation of people in urban green spaces on workdays tends to vary more in time and be more concentrated in space, while the highest usage is more stable on weekends. More importantly, the percentage of weekday green space utilization is higher in small parks and green strips in the city, with the density increasing in those small areas, while the green space at a greater distance to the city center is underutilized. This study validates the potential of applying Baidu Heat Map data to provide a dynamic perspective of green space use, and highlights the need for more green space in city centers

SRMS as a Novel Therapeutic Target in Gastric Cancer Peritoneal Metastases

https://openworks.mdanderson.org/sumexp21/1233/thumbnail.jp

COX-2 induction by unconjugated bile acids involves reactive oxygen speciesmediated signalling pathways in Barrett's oesophagus and oesophageal adenocarcinoma

Objectives: Bile reflux contributes to oesophageal injury and neoplasia. COX-2 is involved in both inflammation and carcinogenesis; however, the precise mechanisms by which bile acids promote COX-2 expression in the oesophagus are largely unknown. We analysed the molecular mechanisms that govern bile acid-mediated expression of COX-2 in Barrett's oesophagus and oesophageal adenocarcinoma (OA). Design: The effects of bile acids on COX-2 expression were analysed in immortalised Barrett's oesophagus and OA cells using immunoblotting and transient transfections. Pharmacological inhibitors, phospho-specific antibodies, dominant-negative mutants and siRNA techniques were used to identify relevant signalling pathways. Flow cytometry and reactive oxygen species (ROS) scavengers were used to examine ROS involvement. Immunohistochemistry was performed on oesophageal mucosa obtained from an established rat model of bile reflux. Results: Unconjugated bile acids potently stimulated COX-2 expression and induced AKT and ERK1/2 phosphorylation in concert with COX-2 induction. These findings were mimicked in the in vivo rat model. Dominant-negative (DN) AKT and LY294002 (PI3K inhibitor) or U0126 (MEK-1/2 inhibitor) blocked chenodeoxycholic acid (CD) and deoxycholic acid (DC) mediated COX-2 induction. CD and DC also induced CREB phosphorylation and AP-1 activity. CREB-specific siRNA and DN AP-1 blocked CD and DC-induced COX-2 induction. Finally, CD and DC increased intracellular ROS, while ROS scavengers blocked COX-2 induction and the signalling pathways involved. Conclusions: Unconjugated bile acids induce CREB and AP-1-dependent COX-2 expression in Barrett's oesophagus and OA through ROS-mediated activation of PI3K/AKT and ERK1/2. This study enhances our understanding of the molecular mechanisms by which bile acids promote the development of oesophageal adenocarcinoma

Type-A quasi-periodic oscillation in the black hole transient MAXI J1348-630

We present a detailed analysis of the spectral and timing characteristics of a 7-Hz type-A quasi-periodic oscillation (QPO) detected in NICER observations of the black hole X-ray binary MAXI J1348-630 during its high-soft state. The QPO is broad and weak, with an integrated fractional rms amplitude of 0.9 per cent in the 0.5-10 keV band. Thanks to the large effective area of NICER, combined with the high flux of the source and a relatively long accumulative exposure time, we construct the first rms and phase-lag spectra for a type-A QPO. Our analysis reveals that the fractional rms amplitude of the QPO increases with energy from below 1 per cent at 1 keV to 3 per cent at 6 keV. The shape of the QPO spectrum is similar to that of the Comptonised component, suggesting that the Comptonised region is driving the variability. The phase lags at the QPO frequency are always soft taking the lowest energy as reference. By jointly fitting the time-averaged spectrum of the source and the rms and phase-lag spectra of the QPO with the time-dependent Comptonisation model vkompthdk, we find that the radiative properties of the type-A QPO can be explained by a vertically extended Comptonised region with a size of 2300 km.Comment: 7 pages, 5 figures, accepted for publication in MNRA

Proteogenomic Landscape of Gastric Adenocarcinoma Peritoneal Metastases

Advanced gastric adenocarcinoma (GAC) often leads to peritoneal carcinomatosis (PC) and is associated with very poor outcome. Here we report the comprehensive proteogenomic study of ascites derived cells from a prospective GAC cohort (n = 26 patients with peritoneal carcinomatosis, PC). A total of 16,449 proteins were detected from whole cell extracts (TCEs). Unsupervised hierarchical clustering resulted in three distinct groups that reflected extent of enrichment in tumor cells. Integrated analysis revealed enriched biological pathways and notably, some druggable targets (cancer-testis antigens, kinases, and receptors) that could be exploited to develop effective therapies and/or tumor stratifications. Systematic comparison of expression levels of proteins and mRNAs revealed special expression patterns of key therapeutics target notably high mRNA and low protein expression of HAVCR2 (TIM-3), and low mRNA but high protein expression of cancer-testis antigens CTAGE1 and CTNNA2. These results inform strategies to target GAC vulnerabilities

Type-A quasi-periodic oscillation in the black hole transient MAXI J1348-630

We present a detailed analysis of the spectral and timing characteristics of a 7-Hz type-A quasi-periodic oscillation (QPO) detected in NICER observations of the black hole X-ray binary MAXI J1348-630 during its high-soft state. The QPO is broad and weak, with an integrated fractional rms amplitude of 0.9 per cent in the 0.5-10 keV band. Thanks to the large effective area of NICER, combined with the high flux of the source and a relatively long accumulative exposure time, we construct the first rms and phase-lag spectra for a type-A QPO. Our analysis reveals that the fractional rms amplitude of the QPO increases with energy from below 1 per cent at 1 keV to ∼3 per cent at 6 keV. The shape of the QPO spectrum is similar to that of the Comptonized component, suggesting that the Comptonized region is driving the variability. The phase lags at the QPO frequency are always soft taking the lowest energy as reference. By jointly fitting the time-averaged spectrum of the source and the rms and phase-lag spectra of the QPO with the time-dependent Comptonization model vkompthdk, we find that the radiative properties of the type-A QPO can be explained by a vertically extended Comptonized region with a size of ∼2300 km.</p

Galectin-3 synergizes with CD47 to Suppress Phagocytosis and T cell immunity in Peritoneal Metastases of Gastric Adenocarcinoma

View full abstracthttps://openworks.mdanderson.org/leading-edge/1061/thumbnail.jp

Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T-cell Immunity in Gastric Cancer Peritoneal Metastases

UNLABELLED: The peritoneal cavity is a common site of gastric adenocarcinoma (GAC) metastasis. Peritoneal carcinomatosis (PC) is resistant to current therapies and confers poor prognosis, highlighting the need to identify new therapeutic targets. CD47 conveys a don\u27t eat me signal to myeloid cells upon binding its receptor signal regulatory protein alpha (SIRPα), which helps tumor cells circumvent macrophage phagocytosis and evade innate immune responses. Previous studies demonstrated that the blockade of CD47 alone results in limited clinical benefits, suggesting that other target(s) might need to be inhibited simultaneously with CD47 to elicit a strong antitumor response. Here, we found that CD47 was highly expressed on malignant PC cells, and elevated CD47 was associated with poor prognosis. Galectin-3 (Gal3) expression correlated with CD47 expression, and coexpression of Gal3 and CD47 was significantly associated with diffuse type, poor differentiation, and tumor relapse. Depletion of Gal3 reduced expression of CD47 through inhibition of c-Myc binding to the CD47 promoter. Furthermore, injection of Gal3-deficient tumor cells into either wild-type and Lgals3-/- mice led to a reduction in M2 macrophages and increased T-cell responses compared with Gal3 wild-type tumor cells, indicating that tumor cell-derived Gal3 plays a more important role in GAC progression and phagocytosis than host-derived Gal3. Dual blockade of Gal3 and CD47 collaboratively suppressed tumor growth, increased phagocytosis, repolarized macrophages, and boosted T-cell immune responses. These data uncovered that Gal3 functions together with CD47 to suppress phagocytosis and orchestrate immunosuppression in GAC with PC, which supports exploring a novel combination therapy targeting Gal3 and CD47. SIGNIFICANCE: Dual inhibition of CD47 and Gal3 enhances tumor cell phagocytosis and reprograms macrophages to overcome the immunosuppressive microenvironment and suppress tumor growth in peritoneal metastasis of gastric adenocarcinoma

High energy Millihertz quasi-periodic oscillations in 1A 0535+262 with Insight-HXMT challenge current models

We studied the millihertz quasi-periodic oscillation (mHz QPO) in the 2020 outburst of the Be/X-ray binary 1A 0535+262 using Insight-HXMT data over a broad energy band. The mHz QPO is detected in the 27-120 keV energy band. The QPO centroid frequency is correlated with the source flux, and evolves in the 35-95 mHz range during the outburst. The QPO is most significant in the 50-65 keV band, with a significance of ~ 8 sigma, but is hardly detectable (<2 sigma) in the lowest (1-27 keV) and highest (>120 keV) energy bands. Notably, the detection of mHz QPO above 80 keV is the highest energy at which mHz QPOs have been detected so far. The fractional rms of the mHz QPO first increases and then decreases with energy, reaching the maximum amplitude at 50-65 keV. In addition, at the peak of the outburst, the mHz QPO shows a double-peak structure, with the difference between the two peaks being constant at ~0.02 Hz, twice the spin frequency of the neutron star in this system. We discuss different scenarios explaining the generation of the mHz QPO, including the beat frequency model, the Keplerian frequency model, the model of two jets in opposite directions, and the precession of the neutron star, but find that none of them can explain the origin of the QPO well. We conclude that the variability of non-thermal radiation may account for the mHz QPO, but further theoretical studies are needed to reveal the physical mechanism.Comment: 13 pages, 7 figures. Accepted for publication in MNRA

Clinically Conserved Genomic Subtypes of Gastric Adenocarcinoma

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions