Hypoxia is a common condition found in a wide range of solid tumors and is often associated with poor prognosis. Hypoxia increases tumor glycolysis, angiogenesis, and other survival responses, as ...well as invasion and metastasis by activating relevant gene expressions through hypoxia-inducible factors (HIF). HIF-1α and HIF-2α undergo oxygen-dependent regulation, and their overexpression is frequently associated with metastasis and poor clinical outcomes. Recent studies show that each step of the metastasis process, from the initial epithelial-mesenchymal transition to the ultimate organotropic colonization, can potentially be regulated by hypoxia, suggesting a master regulator role of hypoxia and HIFs in metastasis. Furthermore, modulation of cancer stem cell self-renewal by HIFs may also contribute to the hypoxia-regulated metastasis program. The hypoxia-induced metastatic phenotype may be one of the reasons for the modest efficacy of antiangiogenic therapies and may well explain the recent provocative findings that antiangiogenic therapy increased metastasis in preclinical models. Multiple approaches to targeting hypoxia and HIFs, including HIF inhibitors, hypoxia-activated bioreductive prodrugs, and gene therapies may become effective treatments to prevent or reduce metastasis.
Although photons in free space barely interact, matter can mediate interactions between them resulting in optical nonlinearities. Such interactions at the single-quantum level result in an on-site ...photon repulsion, crucial for photon-based quantum information processing and for realizing strongly interacting many-body states of light. Here, we report repulsive dipole-dipole interactions between electric field-tuneable, localized interlayer excitons in the MoSe
/WSe
heterobilayer. The presence of a single, localized exciton with an out-of-plane, non-oscillating dipole moment increases the energy of the second excitation by ~2 meV-an order of magnitude larger than the emission linewidth and corresponding to an inter-dipole distance of ~7 nm. At higher excitation power, multi-exciton complexes appear at systematically higher energies. The magnetic field dependence of the emission polarization is consistent with the spin-valley singlet nature of the dipolar molecular state. Our finding represents a step towards the creation of excitonic few- and many-body states such as dipolar crystals with spin-valley spinor in van der Waals heterostructures.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Interfering with intratumoral metabolic processes is proven to effectively sensitize different antitumor treatments. Here, a tumor‐targeting catalytic nanoplatform (CQ@MIL‐GOX@PB) loading with ...autophagy inhibitor (chloroquine, CQ) and glucose oxidase (GOX) is fabricated to interfere with the metabolisms of tumor cells and tumor‐associated macrophages (TAMs), then realizing effective antitumor chemodynamic therapy (CDT). Once accumulating in the tumor site with the navigation of external biotin, CQ@MIL‐GOX@PB will release Fe ions and CQ in the acid lysosomes of tumor cells, the latter can sensitize Fe ions‐involved antitumor CDT by blocking the autophagy‐dependent cell repair. Meanwhile, the GOX component will consume glucose, which not only generates many H2O2 for CDT but also once again decelerates the tumor repair process by reducing energy metabolism. What is more, the release of CQ can also drive the NO anabolism of TAMs to further sensitize CDT. This strategy of multiple metabolic regulations is evidenced to significantly improve the antitumor effect of traditional CDT nanoagents and might provide a new sight to overcome the bottlenecks of different antitumor treatments.
The tumor‐targeting multiple metabolic regulations are performed by the CQ@MIL‐GOX@PB nanosystem to achieve effective antitumor chemodynamic therapy (CDT). By promoting the NO anabolism of tumor‐associated macrophages, and inhibiting energy metabolism and autophagy of tumor cells, the CDT effect of CQ@MIL‐GOX@PB is burst via the multiple sensitization mechanisms.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We propose an experimentally feasible method for enhancing the atom-field coupling as well as the ratio between this coupling and dissipation (i.e., cooperativity) in an optical cavity. It exploits ...optical parametric amplification to exponentially enhance the atom-cavity interaction and, hence, the cooperativity of the system, with the squeezing-induced noise being completely eliminated. Consequently, the atom-cavity system can be driven from the weak-coupling regime to the strong-coupling regime for modest squeezing parameters, and even can achieve an effective cooperativity much larger than 100. Based on this, we further demonstrate the generation of steady-state nearly maximal quantum entanglement. The resulting entanglement infidelity (which quantifies the deviation of the actual state from a maximally entangled state) is exponentially smaller than the lower bound on the infidelities obtained in other dissipative entanglement preparations without applying squeezing. In principle, we can make an arbitrarily small infidelity. Our generic method for enhancing atom-cavity interaction and cooperativities can be implemented in a wide range of physical systems, and it can provide diverse applications for quantum information processing.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Wide bandgap (WB) organic–inorganic hybrid perovskites (OIHPs) with a bandgap ranging between 1.7 and 2.0 eV have shown great potential to improve the efficiency of single‐junction silicon or ...thin‐film solar cells by forming a tandem structure with one of these cells or with a narrow bandgap perovskite cell. However, WB‐OIHPs suffer from a large open‐circuit voltage (Voc) deficit in photovoltaic devices, which is associated with the phase segregation of the materials under light illumination. In this work the photoinstability is demonstrated and Voc loss can be addressed by combining grain crystallization and grain boundary passivation, achieved simultaneously through tuning of perovskite precursor composition. Using FA0.17Cs0.83PbI3–xBrx (x = 0.8, 1.2 1.5, and 1.8), with a varied bandgap from 1.72 to 1.93 eV, as the model system it is illustrated how precursor additive Pb(SCN)2 should be matched with a proper ratio of FAX (I and Br) to realize large grains with defect‐healed grain boundaries. The optimized WB‐OIHPs show good photostability at both room‐temperature and elevated temperature. Moreover, the corresponding solar cells exhibit excellent photovoltaic performances with the champion Voc/stabilized power output efficiency reaching 1.244 V/18.60%, 1.284 V/16.51%, 1.296 V/15.01%, and 1.312 V/14.35% for WB‐OIHPs with x = 0.8, 1.2, 1.5, and 1.8, respectively.
The photoinduced phase segregation in wide bandgap hybrid perovskites are greatly suppressed by combining grain crystallization and grain boundary passivation. As a result, the open‐circuit voltage (Voc) loss of the corresponding devices is highly reduced, demonstrating a monotonic increase of Voc with increasing of bandgap from 1.72 to 1.93 eV.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In this study, bandgap of the two‐dimensional (2D) TiO2, a transition‐metal oxide, was obtained by the diffusion Monte Carlo (DMC) method for the first time. This genuine 2D monolayer material that ...includes transition elements has been proven to be very challenging for reliable prediction of the bandgap. In order to improve the description of correlation effects, the DMC method was used to calculate the bandgaps of 2D‐TiO2 in α‐ and β‐phases, and the obtained results were compared with the density functional theory (DFT) calculations. The DMC results obtained from the infinite periodic superlattices predict ∆f of the 2D‐TiO2 in the α‐ and β‐phases to be about 5.54(4) and 5.69(2) eV, respectively, indicating that the available DFT results significantly underestimated the bandgaps of 2D‐TiO2 nanosheets. Considering the recently reported linear scaling relationship between the bandgap ∆f and the exciton binding energy ∆e of 2D semiconductors, (∆e ≈ 0.28∆f), the optical bandgap ∆o was further predicted to be ~3.99 eV for the α‐phase TiO2, and it is consistent with the experimental value (~3.84 eV). The successful application of the quantum Monte Carlo (QMC) method on the 2D‐TiO2 systems implies that QMC may serve as a feasible tool to investigate the electronic properties of the freestanding 2D transition‐metal oxides.
This genuine 2D monolayer material that includes transition elements has been proven to be very challenging for reliable prediction of the bandgap. Hence, a more accurate method is urgently needed. The successful application of the QMC method on the 2D‐TiO2 systems implies that QMC may serve as a feasible tool to investigate the electronic properties of the freestanding 2D transition‐metal oxides.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
•LTM, industrial structure optimization and green TFP are integrated into a unified framework.•LTM, industrial structure rationalization and optimization all can improve green TFP, while their ...interactions would inhibit it in China.•There exist regional differences of the impact of LTM and industrial structure on green TFP across the regions in China.
Market-oriented allocation of land resources is one of the main economic reforms in China. However, the influence of land transfer marketization (LTM) on green total factor productivity (green TFP) and its mechanisms remain unknown. Based on panel data of 30 provincial administrative regions in China from 2004 to 2016, this study attempts to establish mechanism among LTM, industrial structure and green TFP, which is measured by the Slack Based Measure DEA (SBM-DEA) model containing undesirable output, and empirically estimates the impact of LTM, the rationalization and optimization of industrial structure and their interactions on green TFP further. The results show that: 1) LTM has a significant promoting effect on the improvement of green TFP in China, and the effect is also significant in the eastern, central and western regions as well, indicating that the application of land transfer policy to regulate regional economic development is widespread in China. 2) The rationalization of industrial structure has significantly promoted the development of green TFP in China, as well as at the regional levels, and the effect decreases from the western region to the central and eastern regions. The optimization of industrial structure also has a promoting effect on green TFP in China and all the regions, but the regional differences of the effect are contrary to that of the rationalization of industrial structure, with a decreasing trend from the eastern region to the central and western regions. 3) The interaction between LTM and the rationalization of industrial structure has significantly inhibited the improvement of green TFP in China, and the regional variations of the restraining effect are higher in the western region, followed by the central and eastern regions. The interaction between LTM and the optimization of industrial structure also has a negative effect on green TFP in China, and the regional variations of the effect showing the decreasing trend from the eastern region to the western and central regions. Therefore, China should continue to adhere to the market-oriented urban land transfer system reform, actively play the role of the government in the industrial upgrading and industrial transfer, and formulate a differentiated land transfer system and industrial development policies based on the economic development and industrial characteristics of various regions, so as to achieve the sustainable development of China’s economy and society.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Traditionally, conventional microbiological culture methods have been used to detect pathogenic microorganisms in chronic osteomyelitis. However, these methods have been found to have a low detection ...rate, complicating the precise guidance of infection treatment. This study employed metagenomic next-generation sequencing (mNGS) to detect these microorganisms in chronic osteomyelitis with three main objectives: 1). Gain a deeper understanding of the composition of pathogenic microorganisms in chronic osteomyelitis. 2). Compare the microbial detection rates between mNGS and the standard culture methods used in laboratories to enhance the effectiveness of the traditional culture methods. 3). Explore the potential of mNGS in etiological diagnosis. Fifty clinically confirmed intraoperative bone tissue samples of chronic osteomyelitis from January 2021 to December 2021 were collected and subjected to mNGS and microbiological testing, respectively. The orthopaedic surgeon combined clinical manifestations and related examinations to determine the causative pathogens. The culture method obtained 29 aerobic and parthenogenic anaerobic bacteria, 3 specific anaerobic bacteria, and 1 yeast-like fungus. Thirty-six aerobic and parthenogenic anaerobic bacteria, 11 specific anaerobic bacteria, and 1 yeast-like fungus were obtained by mNGS, and 2 Mycobacterium tuberculosis(MTB) strains were detected. However, there was no significant difference in the overall positive detection rate between mNGS and the culture method (P = 0.07), and the two were not statistically significant in detecting aerobic and partly anaerobic bacteria (P = 0.625). But, mNGS was significantly superior to culture in detecting anaerobic bacteria and Mycobacterium tuberculosis (P<0.05). The mNGS method has enhanced our understanding of the distribution of pathogenic microorganisms in chronic osteomyelitis. Traditional culture methods help isolate and cultivate aerobic and facultative anaerobic bacteria, and fungi, and are also utilized for antibacterial drug sensitivity tests. However, mNGS has shown superior capabilities in detecting anaerobic bacteria, MTB, and mixed infection bacteria. This finding offers invaluable guidance for improving laboratory microbial culture and detection conditions. Hence, mNGS should be judiciously used for chronic osteomyelitis, and PCR can be implemented for certain difficult-to-culture microorganisms, such as MTB.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sirtuin 1 (SIRT1), an NAD
-dependent deacetylase, is a key regulator of cellular metabolism. Recent genome-wide association studies identified genetic variants of SIRT1 linked to major depressive ...disorders. SIRT1 is widely expressed in the brain; however, neuronal substrates that mediate SIRT1 action on depressive behaviors remain largely unknown. Here we show that selective deletion of SIRT1 in forebrain excitatory neurons causes depression-like phenotypes in male but not female mice. AAV-Cre-mediated SIRT1 knockdown in the medial prefrontal cortex (mPFC) of adult male mice induces depressive-like behaviors. Whole-cell patch-clamp recordings demonstrate that loss of SIRT1 decreases intrinsic excitability and spontaneous excitatory synaptic transmission in layer V pyramidal neurons in the prelimbic mPFC. Consistent with neuronal hypoexcitability, SIRT1 knockout reduces mitochondrial density and expression levels of genes involved in mitochondrial biogenesis and dynamics in the prelimbic mPFC. When a SIRT1 activator (SRT2104) is injected into the mPFC or lateral ventricle of wild-type mice, it reverses chronic unpredictable stress-induced anhedonia and behavioral despair, indicating an antidepressant-like effect. These results suggest that SIRT1 in mPFC excitatory neurons is required for normal neuronal excitability and synaptic transmission and regulates depression-related behaviors in a sex-specific manner.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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