Under the wave of globalization, some cities in China, especially the so-called “megacities” are entering or have already entered the stage of post-suburbanization. The study places Shanghai suburbs ...in the post-suburbanization landscape and takes Qingpu New Town as an example to systematically analyze the development and formation mechanism of post-suburbanization spaces. This study reveals the features of the post-suburbanization in China as follows. Firstly, In China, post-suburbanization is achieved based on industrialization as well as on the promotion of urbanization. Although urbanization has strengthened other functions of suburban spaces aside from living and production, the production attributes of suburbs remain stable. Secondly, post-suburbanization space with the new town as the development model is an important path for a new round of suburban space growth, it has expanded the space for capital accumulation in metropolitan areas, thus promoting the possibility of reorganizing economic activities within metropolitan areas. At the same time, it focuses on the integration of industries and cities, and the simultaneous development of urbanization and industrialization. In turn, this promotes the accumulation of capital centered on the urban environment and manufacturing production. Furthermore, China’s special institutional circumstance enables its government to organize various actors to form a growth alliance, which will act together in the production of post-suburbanization space.
A yellow long persistent luminescence (LPL) phosphor of CaGa2O4:Bi3+ (CGO:Bi) is developed, of which the LPL can be visually recognized (0.32 mcd m−2) over 36 hours after the removal of the ...excitation source. Furthermore, an excellent LPL performance above the room temperature and unusual thermal quenching behavior are observed. The thermoluminescence (TL) curves indicate that the continuity of the traps structure with different depths is a key factor in ensuring that carriers could be released from deep traps above room temperature successively. The work verifies unambiguously that the continuous defect‐state structure is beneficial to the LPL temperature resistant abilities, which would provide a reasonable approach to design new LPL phosphors in extreme environments.
COVID-19 is a transmissible respiratory disease caused by a novel coronavirus, SARS-CoV-2, and has become a global health emergency. There is an urgent need for robust and practical in vitro model ...systems to investigate viral pathogenesis. Here, we generated human induced pluripotent stem cell (iPSC)-derived lung organoids (LORGs), cerebral organoids (CORGs), neural progenitor cells (NPCs), neurons, and astrocytes. LORGs containing epithelial cells, alveolar types 1 and 2, highly express ACE2 and TMPRSS2 and are permissive to SARS-CoV-2 infection. SARS-CoV-2 infection induces interferons, cytokines, and chemokines and activates critical inflammasome pathway genes. Spike protein inhibitor, EK1 peptide, and TMPRSS2 inhibitors (camostat/nafamostat) block viral entry in LORGs. Conversely, CORGs, NPCs, astrocytes, and neurons express low levels of ACE2 and TMPRSS2 and correspondingly are not highly permissive to SARS-CoV-2 infection. Infection in neuronal cells activates TLR3/7, OAS2, complement system, and apoptotic genes. These findings will aid in understanding COVID-19 pathogenesis and facilitate drug discovery.
Display omitted
•Lung organoids express ACE2/TMPRSS2 and are permissive to SARS-CoV-2 infection•SARS-CoV-2 induces IFNs and cytokines/chemokines, and activates inflammasome pathway•SARS-CoV-2 infection in neurons activates TLR3/7, OAS2, and apoptotic genes•Spike protein and TMPRSS2 inhibitors reduce SARS-CoV-2 infection in organoids
In this report, Rana and colleagues show that human iPSC-derived lung and brain organoids express ACE2/TMPRSS2 and are permissive to SARS-CoV-2 infection inducing specific pathways in lung and brain cells. Spike protein inhibitor, EK1 peptide, and TMPRSS2 inhibitors (camostat/nafamostat) reduced SARS-CoV-2 infection in lung organoids, providing a model system for drug development.
A
bstract
The PandaX-III experiment uses a high-pressure xenon gaseous time projection chamber (TPC) to search for the neutrinoless double beta decay (0
νββ
) of
136
Xe. The absence of the vertex ...position in the electron drift direction at which the event takes place in the detector limits the PandaX-III TPC’s performance. The charged particle tracks recorded by the TPC provide a possibility for vertex reconstruction. In this paper, a convolution neural network (CNN) model VGGZ0net is proposed for the reconstruction of vertex position. An 11 cm precision is achieved with the Monte Carlo simulation events uniformly distributed along a maximum drift distance of 120 cm. The electron loss during the drift under the different gas conditions is studied, and after the distance-based correction, the detector energy resolution is significantly improved. The CNN model is also verified successfully using the experimental data of the PandaX-III prototype detector.
Currently, there is no approved therapy to treat Lassa fever; therefore, repurposing of approved drugs will accelerate the development of a therapeutic stratagem. In this study, we screened an ...FDA-approved library of drugs and identified two compounds, lacidipine and phenothrin, which inhibited Lassa virus entry by blocking low-pH-induced membrane fusion. Additionally, both compounds extended their inhibition against the entry of Guanarito virus, and the viral targets were identified as the SSP-GP2 interface.
ABSTRACT
Lassa virus
(LASV) belongs to the
Mammarenavirus
genus (family
Arenaviridae
) and causes severe hemorrhagic fever in humans. At present, there are no Food and Drug Administration (FDA)-approved drugs or vaccines specific for LASV. Here, high-throughput screening of an FDA-approved drug library was performed against LASV entry by using pseudotype virus bearing LASV envelope glycoprotein (GPC). Two hit compounds, lacidipine and phenothrin, were identified as LASV entry inhibitors in the micromolar range. A mechanistic study revealed that both compounds inhibited LASV entry by blocking low-pH-induced membrane fusion. Accordingly, lacidipine showed virucidal effects on the pseudotype virus of LASV. Adaptive mutant analyses demonstrated that replacement of T40, located in the ectodomain of the stable-signal peptide (SSP), with lysine (K) conferred LASV resistance to lacidipine. Furthermore, lacidipine showed antiviral activity against LASV, the closely related Mopeia virus (MOPV), and the New World arenavirus Guanarito virus (GTOV). Drug-resistant variants indicated that V36M in the ectodomain of the SSP mutant and V436A in the transmembrane domain of the GP2 mutant conferred GTOV resistance to lacidipine, suggesting the interface between SSP and GP2 is the target of lacidipine. This study shows that lacidipine is a candidate for LASV therapy, reinforcing the notion that the SSP-GP2 interface provides an entry-targeted platform for arenavirus inhibitor design.
IMPORTANCE
Currently, there is no approved therapy to treat Lassa fever; therefore, repurposing of approved drugs will accelerate the development of a therapeutic stratagem. In this study, we screened an FDA-approved library of drugs and identified two compounds, lacidipine and phenothrin, which inhibited Lassa virus entry by blocking low-pH-induced membrane fusion. Additionally, both compounds extended their inhibition against the entry of Guanarito virus, and the viral targets were identified as the SSP-GP2 interface.
The economies of China-Japan-Korea （CJK） are complementary, with their proximity resulting in the three countries having a high degree of interdependence with respect to trade. Currently, trade among ...these countries relies mainly on port-centered shipping. The development of the shipping network is integral for in-depth integration of CJK trade. This paper analyzes the overall characteristics, centrality, spatial structure, and vulnerability of the CJK shipping network using the methods of complex network analysis, blocking flow theory, and interruption and deletion of hub ports. The main findings are as follows： 1） The CJK shipping network has a small average path length and clustering coefficient, and its degree distribution follows a power-law distribution, which make the network present obvious characteristics of a Barabasi-Albert scale-free. 2） The characteristics of the multi-center point of the CJK shipping network can alleviate traffic pressure. At the same time, the network shows a clear hierarchy in the port transportation system, with cargo transport relying mainly on the ‘hub port-hub port＇ connection. 3） The CJK shipping network is relatively stable. Compared with ports in Japan and Korea, the main hub ports in China have a greater impact on the stability of the shipping network, in particular those ports of the central coastal region, including Shanghai, Ningbo, and Lianyungang.
Bone defects, as one of the most urgent problems in the orthopedic clinic, have attracted much attention from the biomedical community and society. Hydrogels have been widely used in the biomedical ...field for tissue engineering research because of their excellent hydrophilicity, biocompatibility, and degradability. Stimulus-responsive hydrogels, as a new type of smart biomaterial, have more advantages in sensing external physical (light, temperature, pressure, electric field, magnetic field, etc.), chemical (pH, redox reaction, ions, etc.), biochemical (glucose, enzymes, etc.) and other different stimuli. They can respond to stimuli such as the characteristics of the 3D shape and solid–liquid phase state, and exhibit special properties (injection ability, self-repair, shape memory, etc.), thus becoming an ideal material to provide cell adhesion, proliferation, and differentiation, and achieve precise bone defect repair. This review is focused on the classification, design concepts, and research progress of stimulus-responsive hydrogels based on different types of external environmental stimuli, aiming at introducing new ideas and methods for repairing complex bone defects.
Exosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the ...immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.
Cyanopterus ninghais (Hymenoptera: Braconidae) is a newly discovered parasitoid on the 3rd-5th instar larvae of the Japanese pine sawyer, Monochamus alternatus (Coleoptera: Cerambycidae). We ...investigated the functional response of C. ninghais at three temperatures (20, 25, and 30 °C) and examined mutual interference. Results showed that C. ninghais had a Holling Type II functional response at all temperatures. By increasing the density of the M. alternatus larvae, the number of parasitized larvae increased until a maximum was reached. The parasitoid was most effective (a′/Th) at 30 °C (0.270) and an individual female wasp’s attack rate (a′) was 0.158, the handling time (Th) was 0.587, and the maximum theoretical parasitization rate per day (T/Th) was 11.927. However, the per capita parasitized level and per capita searching efficiency decreased significantly when the parasitoid density ranged from one to five. These findings suggest that intraspecific mutual interference and competition occur when multiple females search for a host in the same area. This study demonstrates that C. ninghais serves as an effective biocontrol agent, displaying strong control capabilities against M. alternatus larvae, with the potential for further development in the context of biological pest management targeting M. alternatus.
Abstract
Cardiorenal syndrome type 4 (CRS4) is a common complication of chronic kidney disease (CKD), but the pathogenic mechanisms remain elusive. Here we report that morphological and functional ...changes in myocardial mitochondria are observed in CKD mice, especially decreases in oxidative phosphorylation and fatty acid metabolism. High phosphate (HP), a hallmark of CKD, contributes to myocardial energy metabolism dysfunction by downregulating peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α). Furthermore, the transcriptional factor interferon regulatory factor 1 (IRF1) is revealed as the key molecule upregulated by HP through histone H3K9 acetylation, and responsible for the HP-mediated transcriptional inhibition of PGC1α by directly binding to its promoter region. Conversely, restoration of PGC1α expression or genetic knockdown of IRF1 significantly attenuates HP-induced alterations in vitro and in vivo. These findings demonstrate that IRF1-PGC1α axis-mediated myocardial energy metabolism remodeling plays a crucial role in the pathogenesis of CRS4.
PDF
