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Translation control of proinflammatory genes has a crucial role in regulating the inflammatory response and preventing chronic inflammation, including a transition to cancer. The proinflammatory tumor suppressor protein programmed cell death 4 (PDCD4) is important for maintaining the balance between inflammation and tumorigenesis. PDCD4 messenger RNA translation is inhibited by the oncogenic microRNA, miR-21. AU-rich element-binding protein HuR was found to interact with the PDCD4 3′-untranslated region (UTR) and prevent miR-21-mediated repression of PDCD4 translation. Cells stably expressing miR-21 showed higher proliferation and reduced apoptosis, which was reversed by HuR expression. Inflammatory stimulus caused nuclear-cytoplasmic relocalization of HuR, reversing the translation repression of PDCD4. Unprecedentedly, HuR was also found to bind to miR-21 directly, preventing its interaction with the PDCD4 3′-UTR, thereby preventing the translation repression of PDCD4. This suggests that HuR might act as a ‘miRNA sponge‘ to regulate miRNA-mediated translation regulation under conditions of stress-induced nuclear-cytoplasmic translocation of HuR, which would allow fine-tuned gene expression in complex regulatory environments.

3D electrode design is normally opted for multiple advantages, however, instability/detachment of active material causes the pulverization and degradation of the structure, and ultimately poor cyclic stability. Here, a dually protected, highly compressible, and freestanding anode is presented for sodium‐ion batteries, where 3D carbon nanotube (CNT) sponge is decorated with homogeneously dispersed CoSe2 nanoparticles (NPs) which are protected under carbon overcoat (CNT/CoSe2/C). The 3D CNT sponge delivers enough space for high mass loading while providing high mechanical strength and faster conduction pathway among the NPs. The outer amorphous carbon overcoat controls the formation of solid electrolyte interphase film by avoiding direct contact of CoSe2 with electrolyte, accommodates large volume changes, and ultimately enhances the overall conductivity of cell and assists in transmitting electron to an external circuit. Moreover, the hybrid can be densified up to 11‐fold without affecting its microstructure that results in ultrahigh areal mass loading of 17.4 mg cm−2 and an areal capacity of 7.03 mAh cm−2 along with a high gravimetric capacity of 531 mAh g−1 at 100 mA g−1. Thus, compact and smart devices can be realized by this new electrode design for heavy‐duty commercial applications. A 3D and dually protected electrode design (carbon nanotube (CNT)/CoSe2/C) is presented in which a CNT sponge is decorated with CoSe2 nanoparticles and then externally protected with carbon layers. The representative 3D CNT/CoSe2/C heterostructure has the ability to be densified without influencing its microstructure that results in high areal capacity along with high gravimetric capacity for sodium‐ion batteries.

Searching for periodic non-accelerated signals in the presence of ideal white noise using the fully phase-coherent fast-folding algorithm (FFA) is theoretically established as a more sensitive search method than the fast Fourier transform (FFT) search with incoherent harmonic summing. In this paper, we present a comparison of the performance of an FFA search implementation using RIPTIDE and an FFT search implementation using PRESTO, over a range of signal parameters with white noise and with real telescope noise from the Giant Meterwave Radio Telescope (GMRT) High Resolution Southern Sky (GHRSS) survey with the upgraded GMRT (uGMRT). We find that the FFA search with appropriate de-reddening of the time series performs better than the FFT search with spectral whitening for long-period pulsars under real GHRSS noise conditions. We describe an FFA-search pipeline implemented for the GHRSS survey looking for pulsars over a period of 0.1–100 s and up to a dispersion measure of 500 pc cm−3. We processed GHRSS survey data covering ∼1500 deg2 of the sky with this pipeline. We re-detected 43 known pulsars with a better signal-to-noise ratio in the FFA search than in the FFT search. We also report the discovery of two new pulsars, including a long-period pulsar with a short duty cycle, using this FFA-search pipeline. A population of long-period pulsars with periods of several seconds or higher could help constrain the pulsar death line.

We report the discovery of three millisecond pulsars (MSPs): PSRs J1120−3618, J1646−2142, and J1828+0625 with the Giant Metrewave Radio Telescope (GMRT) at a frequency of 322 MHz using a 32 MHz observing bandwidth. These sources were discovered serendipitously while conducting the deep observations to search for millisecond radio pulsations in the directions of unidentified Fermi Large Area Telescope (LAT) γ-ray sources. We also present phase coherent timing models for these MSPs using ∼5 yr of observations with the GMRT. PSR J1120−3618 has a 5.5 ms spin period and is in a binary system with an orbital period of 5.6 days and minimum companion mass of 0.18 M ⊙, PSR J1646−2142 is an isolated object with a spin period of 5.8 ms, and PSR J1828+0625 has a spin period of 3.6 ms and is in a binary system with an orbital period of 77.9 days and minimum companion mass of 0.27 M ⊙. The two binaries have very low orbital eccentricities, in agreement with expectations for MSP-helium white dwarf systems. Using the GMRT 607 MHz receivers having a 32 MHz bandwidth, we have also detected PSR J1646−2142 and PSR J1828+0625, but not PSR J1120−3618. PSR J1646−2142 has a wide profile, with significant evolution between 322 and 607 MHz, whereas PSR J1120−3618 exhibits a single peaked profile at 322 MHz and PSR J1828+0625 exhibits a single peaked profile at both the observing frequencies. These MSPs do not have γ-ray counterparts, indicating that these are not associated with the target Fermi LAT pointing emphasizing the significance of deep blind searches for MSPs.

We discovered four millisecond pulsars (MSPs) in searches of 80 γ-ray sources conducted from 2015 to 2017 with the Murriyang radio telescope of the Parkes Observatory. We provide an overview of the survey and focus on the results of a follow-up pulsar timing campaign. Using Fermi Large Area Telescope data, we have detected γ-ray pulsations from all four pulsars, and by combining radio and γ-ray data, we obtain improved timing solutions. We also provide flux density distributions for the radio pulsars and flux-calibrated and phase-aligned radio and γ-ray pulse profiles. Some of the pulsars may be suitable for radio pulsar timing array experiments. PSR J0646–5455, PSR J1803–4719, and PSR J2045–6837 are in typical, nearly circular white dwarf binaries with residual eccentricities proportional to their binary periods. PSR J1833–3840 is a black widow pulsar with the longest known period, Pb = 0.9 day, and a very soft radio spectrum. PSR J0646–5455 has a strong, Vela-like γ-ray pulse profile and is suitable for inclusion in the γ-ray pulsar timing array. Despite this, it is possibly one of the lowest-efficiency γ-ray MSPs known. Indeed, all four new γ-ray MSPs have lower-than-average efficiency, a potential indication of bias in earlier searches. Finally, we retrospectively evaluate the efficiency of this survey: while only four new MSPs were directly discovered, subsequent campaigns have found pulsars in a further 19 of our targets, an excellent 30% efficiency.

Immunologically inert or cold tumors pose a substantial challenge to the effectiveness of immunotherapy. The use of oncolytic viruses (OVs) to induce immunogenic cell death (ICD) in tumor cells is a well-established strategy for initiating the cancer immunity cycle (CIC). This process promotes the trafficking and infiltration of CD8+ T cells into tumors, thereby eliciting a tumor-specific immune response. Despite the potential of OVs for handling cold tumors, clinical outcomes have fallen short of expectations. To better understand the obstacles faced by oncolytic virus immunotherapy (OVI), we would like to revisit the OV issue. Growing evidence indicates that limited intratumoral penetration and inadequate intratumoral distribution of OVs are critical factors contributing to the suboptimal response to OVI. Aberrant expressions of matrix proteins by cancer-associated fibroblasts (CAFs) alter the mechanical properties of the tumor extracellular matrix (ECM). This results in increased ECM desmoplasia and elevated intratumoral interstitial fluid pressure (IFP), creating physical barriers that impede the penetration and dissemination of OVs within tumors. This review explores the latest advancements in strategies designed to improve the intratumoral penetration of OVs to facilitate the penetration of tumor-infiltrating lymphocytes (TILs) into cold tumors. Additionally, we investigated current clinical trials and challenges associated with translating these strategies into clinical practice to improve patient outcomes.

We have searched for radio pulsations toward 49 Fermi Large Area Telescope (LAT) 1FGL Catalog γ-ray sources using the Green Bank Telescope at 350 MHz. We detected 18 millisecond pulsars (MSPs) in blind searches of the data; 10 of these were discoveries unique to our survey. 16 are binaries, with eight having short orbital periods P B < 1 day. No radio pulsations from young pulsars were detected, although three targets are coincident with apparently radio-quiet γ-ray pulsars discovered in LAT data. Here, we give an overview of the survey and present radio and γ-ray timing results for the 10 MSPs discovered. These include the only isolated MSP discovered in our survey and six short-P B binary MSPs. Of these, three have very-low-mass companions (M c ≪ 0.1 M ⊙) and hence belong to the class of black widow pulsars. Two have more massive, nondegenerate companions with extensive radio eclipses and orbitally modulated X-ray emission consistent with the redback class. Significant γ-ray pulsations have been detected from nine of the discoveries. This survey and similar efforts suggest that the majority of Galactic γ-ray sources at high Galactic latitudes are either MSPs or relatively nearby nonrecycled pulsars, with the latter having on average a much smaller radio/γ-ray beaming ratio as compared to MSPs. It also confirms that past surveys suffered from an observational bias against finding short-P B MSP systems.

The 559 Hz black-widow pulsar PSR J1555−2908, originally discovered in radio, is also a bright gamma-ray pulsar. Timing its pulsations using 12 yr of Fermi-Large Area Telescope gamma-ray data reveals long-term variations in its spin frequency that are much larger than is observed from other millisecond pulsars. While this variability in the pulsar rotation rate could be intrinsic “timing noise,” here we consider an alternative explanation: the variations arise from the presence of a very-low-mass third object in a wide multiyear orbit around the neutron star and its low-mass companion. With current data, this hierarchical-triple-system model describes the pulsar’s rotation slightly more accurately than the best-fitting timing noise model. Future observations will show if this alternative explanation is correct.

Circulating endothelial cells (CECs) are widely reported as a promising biomarker of endothelial damage/dysfunction in coronary artery disease (CAD). The two popular methods of CEC quantification include the use of immunomagnetic beads separation (IB) and flow cytometry analysis (FC); however, they suffer from two main shortcomings that affect their diagnostic and prognostic responses: non-specific bindings of magnetic beads to non-target cells and a high degree of variability in rare cell identification, respectively. We designed a microfluidic chip with spatially staggered micropillars for the efficient harvesting of CECs with intact cellular morphology in an attempt to revisit the diagnostic goal of CEC counts in CAD patients with angina pectoris. A label-free microfluidic assay that involved an in-situ enumeration and immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs was carried out to assess the CEC count in human peripheral blood samples. A total of 55 CAD patients with angina pectoris [16 with chronic stable angina (CSA) and 39 with unstable angina (UA)], together with 15 heathy controls (HCs) were enrolled in the study. CEC counts are significantly higher in both CSA and UA groups compared to the HC group [respective medians of 6.9, 10.0 and 1.5 cells/ml (p < 0.01)]. Further, a significant elevation of CEC count was observed in the three UA subgroups [low risk (5.3) vs. intermediate risk (10.8) vs. high risk (18.0) cells/ml, p < 0.001) classified in accordance to the TIMI NSTEMI/UA risk score system. From the receiver-operating characteristic curve analysis, the AUCs for distinguishing CSA and UA from HC were 0.867 and 0.938, respectively. The corresponding sensitivities were 87.5% and 84.6% and the specificities were 66.7% and 86.7%, respectively. Our microfluidic assay system is efficient and stable for CEC capture and enumeration. The results showed that the CEC count has the potential to be a promising clinical biomarker for the assessment of endothelial damage/dysfunction in CAD patients with angina pectoris.

Neutron Star Interior Composition Explorer (NICER) data have been used to estimate the masses and radii of the rotation-powered millisecond pulsars PSR J0030+0451, PSR J0740+6620, PSR J0437−4715, PSR J1231−1411, and PSR J0614−3329, sometimes in joint analyses with XMM-Newton data. These measurements provide invaluable information about the properties of cold, catalyzed matter beyond nuclear saturation density. Here, we present the results of our modeling of NICER data on PSR J0437−4715 using several different models of hot thermal X-ray-emitting spots on the stellar surface. For this pulsar, previous Nuclear Spectroscopic Telescope Array observations established that there is also a modulated nonthermal component to the emission, but the previously published analysis of NICER data did not model this component. We find that the Bayesian evidence is significantly higher when the modulated nonthermal component is included and that omission of this component leads to poorer fits to the bolometric NICER data and thus risks bias in the resulting radius estimates. Our models, which we pursue to inferential convergence, therefore have modulated nonthermal emission, and our headline model has in addition three uniform-temperature thermally emitting circular spots. Using this model, the symmetric 68% credible range in the radius is 11.9–15.5 km, which at the independently measured mass of M = 1.418 ± 0.044 M⊙ is consistent with previous reports of the radius of the ∼1.4 M⊙ pulsar PSR J0030+0451. We discuss the implications of this measurement for the equation of state of dense matter.