Co-delivery of gemcitabine and Triapine by calcium carbonate nanoparticles against chemoresistant pancreatic cancer

Pancreatic cancer is a malignant disease with high mortality, and its systemic treatment strategy mainly focuses on chemotherapy. Yet, the overall prognosis of pancreatic cancer patients is still extremely poor with a low survival rate. Gemcitabine (GEM) is a widely used chemotherapeutic agent for the treatment of pancreatic cancer. However, GEM chemoresistance remains the major challenge. In this study, we prepared calcium carbonate nanoparticles (CaCO3 NPs) loaded with a nucleotide reductase inhibitor (Triapine) and GEM to suppress the GEM resistance of pancreatic cancer cells (PANC-1/GEM) and solve the problem of poor solubility of Triapine. CaCO3-GEM-Triapine NPs nano-formulations enhanced the therapeutic effect of GEM-based chemotherapy by inhibiting cancer cell proliferation, migration, and resistance to GEM using both 2D PANC-1/GEM cells and 3D tumor spheroids. The study indicated that CaCO3 NPs loaded with GEM and Triapine could provide an effective treatment option to overcome drug resistance in pancreatic cancer

New genus and species of lice in the Oxylipeurus-complex (Phthiraptera, Ischnocera, Philopteridae), with an overview of the distribution of ischnoceran chewing lice on galliform hosts

Here, we describe a new genus of lice (Phthiraptera, Ischnocera) in the Oxylipeurus-complex, parasitising galliform hosts in the genera Tragopan Cuvier, 1829. This genus, Pelecolipeurus gen. nov., is separated from other members of the complex by the unique shape of the male subgenital plate and stylus, the male genitalia and other characters. The only previously-known species in the genus is Lipeurus longus Piaget, 1880, which is here tentatively re-described as Pelecolipeurus longus (Piaget, 1880), based on specimens from a non-type host, Tragopan temminckii (Gray, 1831). In addition, we describe a new species, Pelecolipeurus fujianensis sp. nov., based on specimens from Tragopan caboti (Gould, 1857). An overview of the distribution patterns of ischnoceran lice on galliforms is presented, which suggests that host phylogeny, host biogeography and host biotope, as well as elevation of host range, may all be important factors that have structured louse communities on landfowl. We transfer the genus Afrilipeurus from the Oxylipeurus-complex to the Lipeurus-complex and include an emended key to the Oxylipeurus-complex

Low-mass dark matter search results from full exposure of PandaX-I experiment

We report the results of a weakly-interacting massive particle (WIMP) dark matter search using the full 80.1\;live-day exposure of the first stage of the PandaX experiment (PandaX-I) located in the China Jin-Ping Underground Laboratory. The PandaX-I detector has been optimized for detecting low-mass WIMPs, achieving a photon detection efficiency of 9.6\%. With a fiducial liquid xenon target mass of 54.0\,kg, no significant excess event were found above the expected background. A profile likelihood analysis confirms our earlier finding that the PandaX-I data disfavor all positive low-mass WIMP signals reported in the literature under standard assumptions. A stringent bound on the low mass WIMP is set at WIMP mass below 10\,GeV/c$^2$, demonstrating that liquid xenon detectors can be competitive for low-mass WIMP searches.Comment: v3 as accepted by PRD. Minor update in the text in response to referee comments. Separating Fig. 11(a) and (b) into Fig. 11 and Fig. 12. Legend tweak in Fig. 9(b) and 9(c) as suggested by referee, as well as a missing legend for CRESST-II legend in Fig. 12 (now Fig. 13). Same version as submitted to PR

Activation of Interleukin-1β Release by the Classical Swine Fever Virus Is Dependent on the NLRP3 Inflammasome, Which Affects Virus Growth in Monocytes

Classical swine fever virus (CSFV) is a classic Flavivirus that causes the acute, febrile, and highly contagious disease known as classical swine fever (CSF). Inflammasomes are molecular platforms that trigger the maturation of proinflammatory cytokines to engage innate immune defenses that are induced upon cellular infection or stress. However, the relationship between the inflammasome and CSFV infection has not been thoroughly characterized. To understand the function of the inflammasome response to CSFV infection, we infected porcine peripheral blood monocytes (PBMCs) with CSFV. Our results indicated that CSFV infection induced both the generation of pro-interleukin-1β (pro-IL-1β) and its processing in monocytes, leading to the maturation and secretion of IL-1β through the activation of caspase 1. Moreover, CSFV infection in PBMCs induced the production and cleavage of gasdermin D (GSDMD), which is an inducer of pyroptosis. Additional studies showed that CSFV-induced IL-1β secretion was mediated by NLRP3 and that CSFV infection could sufficiently activate the assembly of the NLRP3 inflammasome in monocytes. These results revealed that CSFV infection inhibited the expression of NLRP3, and knockdown of NLRP3 enhanced the replication of CSFV. In conclusion, these findings demonstrate that the NLRP3 inflammasome plays an important role in the innate immune response to CSFV infection

Investigation on Unsteady Flow Characteristics in an Axial-Flow Fan under Stall Conditions

Based on Shear Stress Transport (SST) turbulence model for unsteady simulation of an axial-flow fan, this paper studies the time-frequency information in the hump region, and investigates the disturbance information of spike and modal wave under different flow coefficients based on continuous wavelet transform (CWT). The results show that before the hump point, the low-frequency modal wave occupies the main disturbance form and circularly propagates at 1/10 of the rotor speed, and the axial-flow fan does not enter the stall stage; while after the flow coefficient reduces to the hump point, the spike wave with higher frequency replaces the modal wave as the main disturbance mode while the axial-flow fan enters the stall stage. Through in-depth investigation of unsteady flow characteristics under the hump point, it is found that after experiencing the emerging spike, with the sharp increase of incidence angle, some flow distortions appear on the intake surface, and further induce some flow paths to form stall vortices. When a path goes into stall stage, the airflow state is greatly affected, the inverse flow and air separation phenomenon in the rim region increase significantly, and the flow capacity decreases significantly, so the flow capacity in the hub region increases correspondingly. The flow path distortion of tip leakage flow (TLF) and leading edge (LE) spillage caused by the stall vortices are the main inducements of rotating stall

Metabolome analysis reveals flavonoid changes during the leaf color transition in Populus × euramericana ‘Zhonghuahongye’

IntroductionTo investigate the mechanism of leaf color change at different stages in Populus × euramericana ‘Zhonghuahongye’ (‘Zhonghong’ poplar).MethodsLeaf color phenotypes were determined and a metabolomic analysis was performed on leaves at three stages (R1, R2 and R3).ResultsThe a*, C* and chromatic light values of the leaves decreased by 108.91%, 52.08% and 113.34%, while the brightness L values and chromatic b* values gradually increased by 36.01% and 13.94%, respectively. In the differential metabolite assay, 81 differentially expressed metabolites were detected in the R1 vs. R3 comparison, 45 were detected in the R1 vs. R2 comparison, and 75 were detected in the R2 vs. R3 comparison. Ten metabolites showed significant differences in all comparisons, which were mostly flavonoid metabolites. The metabolites that were upregulated in the three periods were cyanidin 3,5-O-diglucoside, delphinidin, and gallocatechin, with flavonoid metabolites accounting for the largest proportion and malvidin 3- O-galactoside as the primary downregulated metabolite. The color shift of red leaves from a bright purplish red to a brownish green was associated with the downregulation of malvidin 3-O-glucoside, cyanidin, naringenin, and dihydromyricetin.DiscussionHere, we analyzed the expression of flavonoid metabolites in the leaves of ‘Zhonghong’ poplar at three stages and identified key metabolites closely related to leaf color change, providing an important genetic basis for the genetic improvement of this cultivar

Beam-Membrane Coupled Piezoelectric Micromachined Ultrasonic Transducers with Enhanced Transmitting Sensitivity

Piezoelectric micromachined ultrasonic transducers (PMUTs) are a promising alternative to conventional bulk piezoelectric ceramic-based ultrasonic transducers. However, the transmitting sensitivity of the reported PMUTs is far from satisfactory. In this paper, we report a beam-membrane coupled PMUT (BM-PMUT), which enhances the transmitting sensitivity via simultaneously increasing the acoustic emission areas and maintaining the comparable vibration amplitude. Experimental results show that the center and edge transmitting sensitivities of the BM-PMUT are 108.1 and 96 nm/V at 370 kHz, which are 109.9 and 49.6 nm/V at 677 kHz for the traditional PMUT (T-PMUT). Thus, the BM-PMUT realizes piston-like mode shapes and achieves around twofold improvement in the effective acoustic emission area relative to the traditional T-PMUT of the same size. Due to the larger acoustic emission areas and comparable vibration amplitudes, the normalized far-field sound pressure level of the BM-PMUT is 8.5 dB higher than that of the T-PMUT