Ferroptosis and autophagy are the two forms of the regulation of cell death that play important roles in cancer therapy. However, little is known about the combination of the therapeutic effects of ...ferroptosis and autophagy in cancer therapy. Here, in this study, we constructed a novel carrier-free nanodrug called nanoparticle ferritin-bound erastin and rapamycin (NFER). The NFER nanodrug was prepared by the emulsification technique; it exhibited an average size of 78.8 nm and zeta potential of -25.9 ± 3.3 mV. Controllable drug encapsulation efficiency and loading ratios in NFER could be obtained. This nanodrug showed high stability in both water and PBS for several days. The release studies demonstrated that rapamycin and erastin could reach equilibrium after 24 h and 36 h, respectively; the maximum values of the released percentages of both reached beyond 30%. An in vitro study revealed that NFER showed robust ferroptosis-inducing capability by the downregulation of glutathione peroxidase-4 (GPX4) and lipid peroxidation accumulation. The autophagy process induced by rapamycin in NFER also played an important role in strengthening ferroptosis. The selective cancer cell killing ability of NFER was verified in cancer cells and normal cells. The ferroptosis-induced cytotoxicity was confirmed through several ferroptosis and autophagy inhibitors. Furthermore, the NFER nanodrug showed an improved control of tumor recurrence in the 4T1 tumor resection model. In summary, these results demonstrated that NFER exhibited excellent properties as a nanodrug, and the cell death induced by NFER was through an autophagy-associated ferroptosis pathway. This study based on protein nanodrug-induced autophagy-associated ferroptosis would provide a new insight into cancer therapy.
Abstract
Background
Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an ...effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism.
Results
We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy.
Conclusions
Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.
This study aimed to evaluate the clinical significance of maternally expressed gene 3 in chronic periodontitis. Although previous research has linked long non-coding RNA for maternally expressed gene ...3 to periodontitis, its role in chronic periodontitis remains unclear. Eighty chronic periodontitis patients and 80 healthy subjects were enrolled in this study. Maternally expressed gene 3 levels in the gingival crevicular fluid were quantified through Quantitative Real-Time Reverse Transcription polymerase chain reaction. Additionally, serum proinflammatory cytokines were detected using Enzymelinked Immunosorbent Assay. Statistical analyses, including the chi square test and Pearson correlation, were used to evaluate the relationship between maternally expressed gene 3 levels and periodontitis clinical characteristics. Results indicated a significant decline in maternally expressed gene 3 levels in patients with chronic periodontitis compared to controls. Furthermore, maternally expressed gene 3 was associated with probing pocket depth, attachment loss, plaque index, and bleeding index. Elevated levels of proinflammatory cytokines, negatively correlated with maternally expressed gene 3 abundance, were also observed in patients. These findings suggest that maternally expressed gene 3 downregulation is a characteristic feature of chronic periodontitis, serving as a valuable diagnostic marker. This study contributes to understanding the molecular mechanisms of chronic periodontitis and opens avenues for novel diagnostic modalities. Keywords: Chronic periodontitis, Diagnosis, Gingival crevicular fluid, IncRNA MEG3
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•2D temperature in pulverized coal flame was measured with 1 ms temporal resolution.•Spectroscopic database was corrected by experiment results to improve TDLAS accuracy.•Computed ...tomography reconstruction accuracy of 16-path configuration was evaluated.
Two dimensional temperature and concentration distributions are important parameters for pulverized coal combustion used for power plant to understand the combustion field and develop the high efficient combustion technologies. However, it is difficult to measure two dimensional temperature and concentration in pulverized coal combustion field using conventional measurement technologies because pulverized coal combustion produces lots of dust and strong emission from its flame. This paper focused on the application of two dimensional temperature measurement method based on the combination of computed tomography and tunable diode laser absorption spectroscopy using absorption spectra of water vapor at 1388 nm and 1343 nm for each laser scanning using direct absorption spectroscopy, which show the better characteristics of spatial-temporal resolution, fast response, high sensitivity, self-calibration and optical accessibility. Accuracy of temperature measurement using tunable diode laser absorption spectroscopy was improved by applying the corrected spectroscopic database. Computed tomography reconstruction accuracy of 16 laser-paths configuration was evaluated using sum of squared difference (0.001) and zero-mean normalized cross-correlation (over 0.991), which presented the consistent temperature between assumed and reconstructed distributions. This developed computed tomography-tunable diode laser absorption spectroscopy was successfully applied to pulverized coal flame for two dimensional temperature measurement with 1 ms temporal resolution for time-series two dimensional temperature measurement in the range of 300–2500 K. The rationality was demonstrated by comparison of pulverized coal flame and Methane-Air flame temperature distributions due to the main heat release produced by methane fuel. Its applicability to pulverized coal combustion field will be benefit for optimal operation control and combustion efficiency improvement by combustion organization or new design of combustion system.
Since convolutional neural network (CNN) lacks an inherent mechanism to handle large scale variations, we always need to compute feature maps multiple times for multiscale object detection, which has ...the bottleneck of computational cost in practice. To address this, we devise a recurrent scale approximation (RSA) to compute feature map once only, and only through this map can we approximate the rest maps on other levels. At the core of RSA is the recursive rolling out mechanism: given an initial map on a particular scale, it generates the prediction on a smaller scale that is half the size of input. To further increase efficiency and accuracy, we (a): design a scale-forecast network to globally predict potential scales in the image since there is no need to compute maps on all levels of the pyramid. (b): propose a landmark retracing network (LRN) to retrace back locations of the regressed landmarks and generate a confidence score for each landmark; LRN can effectively alleviate false positives due to the accumulated error in RSA. The whole system could be trained end-to-end in a unified CNN framework. Experiments demonstrate that our proposed algorithm is superior against state-of-the-arts on face detection benchmarks and achieves comparable results for generic proposal generation. The source code of our system is available.
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•A bivariate joint distribution function with high sensitivity of EVI loss to groundwater based on copula.•A stoichiometric chemistry indicator was proposed to reveal the response of ...individual to groundwater at the inter-annual scale.•The vegetation-groundwater response laws from multiple scales were revealed by using multi-source data and multi-technique.•An ecological irrigation model suitable for desert riparian forest was put forward.
Vegetation in arid desert areas plays an extremely important role in maintaining biodiversity and inhibiting desertification. Quantitative understanding of vegetation response to groundwater is essential to priming drought prevention and mitigation, which is a topic that is attracting considerable attention. However, previous studies have rarely assessed the response of vegetation to groundwater from probabilistic or stoichiometric chemical perspective. To address this question, a highly sensitive copula joint distribution of the response of enhanced vegetation index (EVI) loss to groundwater was constructed and a stoichiometric chemistry indicator of the Nitrogen (N) and Phosphorus (P) concentrations in tree rings was innovatively put forward to verify its sensitivity to groundwater. The results obtained revealed that the correlation of EVI with groundwater was better than that with SPEI and TVDI; Furthermore, the critical groundwater thresholds of the EVI loss rate, described as “beginning”, “reaching the maximum”, and “the slowest” were 3.85 m, 6.18–6.75 m, and 7.89 m, respectively. At the inter-annual scale, by measuring the N and P contents of Populus euphratica tree rings, and constructing response model of element contents to groundwater/rainfall, the key thresholds were determined at 5.20–5.31 m and 60 mm, which challenges the traditional understanding that rainfall does not bring ecological benefits to desert riparian forests. To further promote vegetation restoration, based on the response rule of EVI loss and stoichiometric chemical elements of tree rings to groundwater and the intermediate overflow rotation irrigation method, a more advanced desert riparian forest irrigation mode, named “branch-infiltration-rotation-irrigation”, is here proposed.
Phosphate (Pi) starvation response (PHR) transcription factors play key roles in plant Pi homeostasis maintenance. They are negatively regulated by stand-alone SPX proteins, cellular receptors for ...inositol pyrophosphate (PP-InsP) nutrient messengers. How PP-InsP-bound SPX interacts with PHRs is poorly understood. Here, we report crystal structures of the rice SPX2/InsP
/PHR2 complex and of the PHR2 DNA binding (MYB) domain in complex with target DNA at resolutions of 3.1 Å and 2.7 Å, respectively. In the SPX2/InsP
/PHR2 complex, the signalling-active SPX2 assembles into a domain-swapped dimer conformation and binds two copies of PHR2, targeting both its coiled-coil (CC) oligomerisation domain and MYB domain. Our results reveal that the SPX2 senses PP-InsPs to inactivate PHR2 by establishing severe steric clashes with the PHR2 MYB domain, preventing DNA binding, and by disrupting oligomerisation of the PHR2 CC domain, attenuating promoter binding. Our findings rationalize how PP-InsPs activate SPX receptor proteins to target PHR family transcription factors.
Neofusicoccum parvum can cause twig blight of the walnut (Juglans spp.), resulting in great economic losses and ecological damage. We performed proteomic tandem mass tags (TMT) quantification of two ...Neofusicoccum parvum strains with different substrates, BH01 in walnut substrate (SW) and sterile water (SK), and BH03 in walnut substrate (WW) and sterile water (WK), in order to identify differentially expressed proteins. We identified 998, 95, and 489 differentially expressed proteins (DEPs) between the SK vs. WK, SW vs. SK, and WW vs. WK comparison groups, respectively. A phylogenetic analysis was performed to classify the ABC transporter proteins annotated in the TMT protein quantification into eight groups. Physicochemical and structural analyses of the 24 ATP-binding cassette (ABC) transporter proteins revealed that 14 of them had transmembrane structures. To elucidate the functions of these transmembrane proteins, we determined the relative expression levels of ABC transporter genes in strains cultured in sodium chloride, hydrogen peroxide, copper sulfate, and carbendazim mediums, in comparison with pure medium; analysis revealed differential upregulation. To verify the expression results, we knocked out the NpABC2 gene and compared the wild-type and knockout mutant strains. The knockout mutant strains exhibited a higher sensitivity to antifungal drugs. Furthermore, the virulence of the knockout mutant strains was significantly lower than the wild-type strains, thus implying that NpABC2 plays a role in the drug resistance of N. parvum and affects its virulence.
Steel industry is the irreplaceable foundation in heavy industries, which have been developed and improved. The advanced monitoring methods including detection and control technology contribute to ...its development of iron and steel manufacturing processes. With the development of the measurement techniques, laser-induced breakdown spectroscopy (LIBS) has been developed and applied for many industrial fields of elemental monitoring due to the non-contact, fast response, high sensitivity, real-time and multi-dimensional features. The elemental measurement methods in steel industry were summarized and compared in this paper. LIBS measurements of raw material, smelting processes, products, slag, etc. have been reviewed in detail. Challenges for the future of LIBS application in iron and steel making processes have also been discussed. LIBS has a high potential to improve the detection ability of elemental analyses and to promote the on-line monitoring characteristics in iron and steel making plants.
•Components of mixture layer of DCC was experimentally confirmed.•Effect of dissolved non-condensable gas on flow patterns was investigated.•Influence of non-condensable gas on volumetric heat ...transfer coefficient was studied.
An experimental study was performed to investigate the effect of non-condensable gas dissolved in sub-cooled water on steam-water direct contact condensation (DCC). Non-condensable gas dissolved in the sub-cooled water was removed mostly by a degassing membrane device, and the mass fraction of dissolved oxygen was reduced from 7.6 mg/L to 4.6 mg/L and 1.1 mg/L respectively by degassing. Before and after degassing, the flow patterns, thickness of the mixture layer, temperature and pressure distributions, as well as average volumetric heat transfer coefficient were discussed respectively. The visualization results proved that the mixture layer between the water region and steam region mainly consisted of steam, hot water and a small amount of non-condensable gas dissolved out from water at saturated state. Furthermore, the formation mechanism of the mixture layer was qualitatively discussed. Besides, the temperature and pressure distributions on upper and bottom wall were hardly affected by the non-condensable gas dissolved in sub-cooled water. Moreover, the average volumetric heat transfer coefficient was investigated before and after degassing, and it was concluded that the dissolved non-condensable gas had a slight effect on the heat and mass transfer characteristic of DCC process.
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