This paper reports on the observation of the sidereal large-scale anisotropy of cosmic rays using data collected by the ARGO-YBJ experiment over 5 years (2008-2012). This analysis extends previous ...work limited to the period from 2008 January to 2009 December, near the minimum of solar activity between cycles 23 and 24. With the new data sample, the period of solar cycle 24 from near minimum to maximum is investigated. A new method is used to improve the energy reconstruction, allowing us to cover a much wider energy range, from 4 to 520 TeV. Below 100 TeV, the anisotropy is dominated by two wide regions, the so-called "tail-in" and "loss-cone" features. At higher energies, a dramatic change of the morphology is confirmed. The yearly time dependence of the anisotropy is investigated. Finally, no noticeable variation of cosmic-ray anisotropy with solar activity is observed for a median energy of 7 TeV.
Background
IL‐25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the association of IL‐25 with the ...Th2‐biased inflammatory profiles in CRSwNP.
Methods
Nasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL‐25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT‐qPCR, and ELISA. The inflammatory profiles and clinical characteristics of 2 NP subtypes (IL‐25high and IL‐25low) were evaluated, and the effects of IL‐25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro.
Results
The mRNA and protein levels of IL‐25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL‐25high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL‐25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro.
Conclusions
Local IL‐25 plays a crucial role in promoting Th2‐biased inflammatory profiles in NP and may serve as a promising therapeutic target in CRSwNP patients.
Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, ...randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety.
Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P < 0.001) and treatment-related AEs (54.1% versus 90.5%; P < 0.001) were significantly fewer in the icotinib group than in the chemotherapy group.
First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population.
A heterodimer of ultraspiracle (USP) and ecdysone receptor (EcR) mediates 20‐hydroxyecdysone (20E) signalling cascade to regulate insect moulting and metamorphosis. However, at least two questions ...remain to be addressed in terms of the molecular importance of USP in insect species. First, is USP involved in both regulation of ecdysteroidogenesis and mediation of 20E signalling in non‐drosophilid insects, as in Drosophila melanogaster? Second, does USP play any role in larval metamorphosis except as the partner of heterodimeric receptor to activate the downstream 20E signalling genes? In this paper, we found that RNA interference (RNAi) of LdUSP in the final (fourth) instar larvae reduced the messenger RNA levels of four ecdysteroidogenesis genes (Ldspo, Ldphm, Lddib and Ldsad) and 20E titre, and repressed the expression of five 20E signal genes (EcRA, HR3, HR4, E74 and E75) in Leptinotarsa decemlineata. The LdUSP RNAi larvae remained as prepupae, with developing antennae, legs and discs of forewings and hindwings. Dietary supplement with 20E restored the expression of the five 20E signal genes, but only partially alleviated the decreased pupation rate in LdUSP RNAi beetles. Knockdown of LdUSP at the penultimate (third) instar larvae did not affect third–fourth instar moulting. However, silencing LdUSP caused similar but less severe impairments on pupation. Accordingly, we propose that USP is undoubtedly necessary for ecdysteroidogenesis, for mediation of 20E signalling and for initiation of metamorphosis in L. decemlineata.
Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic ...analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region’s hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.
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•A comprehensive cell-type taxonomy is constructed for the entire macaque cortex•Stereo-seq reveals the global distribution of 264 cell types and their marker genes•Regional density and composition of cell types are coupled with cortical hierarchy•Cross-species analysis revealed primate-specific cell types enriched in layer 4
A spatially resolved single-cell transcriptome atlas of macaque cortex is generated that reveals the organization and evolution of primate cortical regions.
High-energy photons from the Crab Nebula
The Crab Nebula contains a pulsar that excites the surrounding gas to emit high-energy radiation. The combination of the pulsar's youth and nearby location ...makes the nebula the brightest gamma-ray source in the sky. The LHAASO Collaboration report observations of this source at energies of tera– to peta–electron volts, extending the spectrum of this prototypical object. They combine these data with observations at lower energies to model the physics of the emission process. The multiwave-length data can be explained by a combination of synchrotron radiation and inverse Compton scattering.
Science
, abg5137, this issue p.
425
Detection of the Crab Nebula at peta–electron volt energies constrains the gamma-ray emission mechanism.
The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar’s rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10
−4
to 1.1 peta–electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta–electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron’s size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta–electron volt electrons, 2.5 × 10
36
ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta–electron volt protons to the production of the highest-energy gamma rays.
Using surface meteorological observation and high-resolution emission data, this paper discusses the application of the PLAM/h index (Parameter Linking Air-quality to Meteorological conditions/haze) ...in the prediction of large-scale low visibility and fog-haze events. Based on the two-dimensional probability density function diagnosis model for emissions, the study extends the diagnosis and prediction of the meteorological pollution index PLAM to the regional visibility fog-haze intensity. The results show that combining the influence of regular meteorological conditions and emission factors together in the PLAM/h parameterization scheme is very effective in improving the diagnostic identification ability of the fog-haze weather in North China. The determination coefficients for four seasons (spring, summer, autumn, and winter) between PLAM/h and visibility observation are 0.76, 0.80, 0.96, and 0.86, respectively, and all of their significance levels exceed 0.001, showing the ability of PLAM/h to predict the seasonal changes and differences of fog-haze weather in the North China region. The high-value correlation zones are located in Jing-Jin-Ji (Beijing, Tianjin, Hebei), Bohai Bay rim, and southern Hebei–northern Henan, indicating that the PLAM/h index is related to the distribution of frequent heavy fog-haze weather in North China and the distribution of emission high-value zone. Through comparative analysis of the heavy fog-haze events and large-scale clear-weather processes in winter and summer, it is found that PLAM/h index 24 h forecast is highly correlated with the visibility observation. Therefore, the PLAM/h index has good capability in identification, analysis, and forecasting.
To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.
Data of chronic phase (CP) and ...accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.
6 893 patients in CP (
=6 453, 93.6%) or AP (
=440, 6.4%) receiving initial imatinib (
=4 906, 71.2%), nilotinib (
=1 157, 16.8%), dasatinib (
=298, 4.3%) or flumatinib (
=532, 7.2%) -therapy. With the median follow-up of 43 (
22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (
=1 055, 15.3%), intolerance (
=248, 3.6%), pursuit of better efficacy (
=168,
To determine the effects of linolenic acid (LNA, 18:3n‐3) in oriental river prawn (Macrobrachium nipponense), an 8‐week feeding experiment was conducted using six isonitrogenous and isoenergetic ...semi‐purified diets containing 0.07 g/kg (control), 7.3 g/kg, 16.6 g/kg, 20.2 g/kg, 27.3 g/kg and 36.3 g/kg LNA. The hepatopancreas lipid content decreased significantly when dietary LNA content was >20.2 g/kg. Fatty acid analysis revealed that the percentage of 18:3n‐3 in the hepatopancreas significantly increased with increasing dietary LNA levels, while 20:5n‐3, 22:5n‐3 and 22:6n‐3 levels in the hepatopancreas decreased in a curvilinear manner as dietary LNA increased. Additionally, qRT‐PCR results revealed that hepatopancreas mRNA expression of acetyl‐CoA carboxylase (ACC) decreased with increasing dietary LNA, while the greatest carnitine palmitoyl transferase‐1(CPT1) mRNA expression was observed in the 2.73 g/kg and 36.3 g/kg groups. Furthermore, hepatopancreas mRNA expression of acyl‐CoA delta‐9 desaturase (SCD) and fatty acyl elongase 6(elovl6) was downregulated when prawns fed the diets containing >20.2 g/kg LNA. These results indicate that dietary 18:3n‐3 could decrease lipid deposition through increased fatty acid β‐oxidation and modulated fatty acid synthesis, and alter fatty acid composition by regulating fatty acyl elongase and fatty acyl desaturase mRNA expression in the M. nipponense.
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