Implantation of hydrogel-liposome nanoplatform inhibits glioblastoma relapse by inducing ferroptosis

Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.

Mutant p53 increases exosome-mediated transfer of mi R-21-3p and mi R-769-3p to promote pulmonary metastasis

Objective: Tumor metastasis is a complex, multistep process that depends on tumor cells and their communication with the tumor microenvironment. A p53 gain-of-function mutant has been shown to enhance the tumorigenesis, invasion, and metastasis abilities of tumor cells. This study aimed to investigate the roles of p53 R273 H mutation in the tumor microenvironment.Methods: The in vitro and in vivo effects of the p53 R273 H mutant on the invasion and metastasis of HCT116 cells were investigated. Exosomes from wild-type and HCT116-TP53(R273 H) cells were cocultured with mouse embryonic fibroblasts(MEFs). The roles of differentially expressed exosomal micro RNAs identified by microarray analysis were investigated. The functions of the p53 R273 H mutant in tumor cells were also investigated via gene expression microarray and quantitative polymerase chain reaction(q PCR) analyses.Results: Introducing p53 R273 H mutant into HCT116 cells significantly potentiated pulmonary metastasis in vivo. In the presence of exosomes derived from HCT116-TP53(R273 H) cells, the exosomes were taken up by MEFs and became activated. Microarray analysis showed that the p53 R273 H mutation increased the exosomal levels of mi R-21-3 p and mi R-769-3 p. Intriguingly, in clinical samples, mi R-21-3 p and mi R-769-3 p levels were significantly higher in patients with a p53 mutation than in those without this mutation. Furthermore, both mi R-21-3 p and mi R-769-3 p activated fibroblasts and exerted a synergistic effect via their target genes on the transforming growth factor-β(TGF-β)/Smad signaling pathway. The activated fibroblasts excreted cytokine TGF-β and may have reciprocally induced cancer cells to undergo epithelial-mesenchymal transition(EMT). Indeed, HCT116-TP53(R273 H) cells showed increased expression of ZEB1 and SNAI2 and decreased transcription of several cell adhesion molecules.Conclusions: The mutant p53-exosomal mi R-21-3 p/mi R-769-3 p-fibroblast-cytokine circuit appears to be responsible for communication between tumor and stromal cells, with exosomal mi RNAs acting as a bridge. mi R-21-3 p and mi R-769-3 p are potential predictive markers of pulmonary metastasis and candidate targets for therapeutic interventions.

An improved transfer learning strategy for short-term cross-building energy prediction usingdata incremental

The available modelling data shortage issue makes it difficult to guarantee the performance of data-driven building energy prediction(BEP)models for both the newly built buildings and existing information-poor buildings.Both knowledge transfer learning(KTL)and data incremental learning(DIL)can address the data shortage issue of such buildings.For new building scenarios with continuous data accumulation,the performance of BEP models has not been fully investigated considering the data accumulation dynamics.DIL,which can learn dynamic features from accumulated data adapting to the developing trend of new building time-series data and extend BEP model's knowledge,has been rarely studied.Previous studies have shown that the performance of KTL models trained with fixed data can be further improved in scenarios with dynamically changing data.Hence,this study proposes an improved transfer learning cross-BEP strategy continuously updated using the coarse data incremental(CDI)manner.The hybrid KTL-DIL strategy(LSTM-DANN-CDI)uses domain adversarial neural network(DANN)for KLT and long short-term memory(LSTM)as the Baseline BEP model.Performance evaluation is conducted to systematically qualify the effectiveness and applicability of KTL and improved KTL-DIL.Real-world data from six-type 36 buildings of six types are adopted to evaluate the performance of KTL and KTL-DIL in data-driven BEP tasks considering factors like the model increment time interval,the available target and source building data volumes.Compared with LSTM,results indicate that KTL(LSTM-DANN)and the proposed KTL-DIL(LSTM-DANN-CDI)can significantly improve the BEP performance for new buildings with limited data.Compared with the pure KTL strategy LSTM-DANN,the improved KTL-DIL strategy LSTM-DANN-CDI has better prediction performance with an average performance improvement ratio of 60%.

The bacterial effector SidN/Lpg1083 promotes cell death by targeting Lamin-B2

To facilitate survival,replication,and dissemination,the intracellular pathogen Legionella pneumophila relies on its unique type IVB secretion system(T4SS)to deliver over 330 effectors to hijack host cell pathways in a spatiotemporal manner.The effectors and their host targets are largely unexplored due to their low sequence identity to the known proteins and functional redundancy.The T4SS effector SidN(Lpg1083)is secreted into host cells during the late infection period.However,to the best of our knowledge,the molecular characterization of SidN has not been studied.Herein,we identified SidN as a nuclear envelope-localized effector.Its structure adopts a novel fold,and the N-terminal domain is crucial for its specific subcellular localization.Furthermore,we found that SidN is transported by eukaryotic karyopherin Importin-13 into the nucleus,where it attaches to the N-terminal region of Lamin-B2 to interfere with the integrity of the nuclear envelope,causing nuclear membrane disruption and eventually cell death.Our work provides new insights into the structure and function of an L.pneumophila effector protein,and suggests a potential strategy utilized by the pathogen to promote host cell death and then escape from the host for secondary infection.

A modelling method for large-scale open spaces orientated toward coordinated control of multiple air-terminal units

The temperature distribution is always assumed to be homogeneous in a traditional singleinput-single-output(SISO)air conditioning control strategy.However,the airflow inside is more complicated and unpredictable.This study proposes a zonal temperature control strategy with a thermal coupling effect integrated for air-conditioned large-scale open spaces.The target space was split into several subzones based on the minimum controllable air terminal units in the proposed method,and each zone can be controlled to its own set-point while considering the thermal coupling effect from its adjacent zones.A numerical method resorting to computational fluid dynamics was presented to obtain the heat transfer coefficients(HTCs)under different air supply scenarios.The relationship between heat transfer coefficient and zonal temperature difference was linearized.Thus,currently available zonal models in popular software can be used to simulate the dynamic response of temperatures in large-scale indoor open spaces.Case studies showed that the introduction of HTCs across the adjacent zones was capable of enhancing the precision of temperature control of large-scale open spaces.It could satisfy the temperature requirements of different zones,improve thermal comfort and at least 11%of energy saving can be achieved by comparing with the conventional control strategy.

Room temperature and humidity decoupling control of common variable air volume air-conditioning system based on bilinear characteristics

Variable air volume(VAV)air-conditioning(AC)systems are widely employed to achieve a comfortable room thermal and humid environment depending on its better regulation performance and energy efficiency.In the single coil VAV AC system,conventional proportional-integral(PI)control algorithm is usually adopted to track the set-points of the room temperature and humidity by regulating the supply air flow rate and the chilled water flow rate,respectively.However,the control performance is usually not good due to the high coupling of the heat and mass transfer in the air-handling unit(AHU).A model-based control method is developed to realize the decoupling control of the room temperature and humidity according to the bilinear characteristics of the temperature and humidity variation.In this control method,a bilinear room temperature controller is used to track the room temperature set-point based on the real-time cooling load,while a room humidity controller is used to track the room humidity set-point depending on the real-time humidity load.The control performance was validated in a simulated VAV AC system.The test results show that comparing with the conventional PI control,the room temperature and humidity are controlled much more robustly and accurately by using the proposed model-based control method.

Exploring the heavy air pollution in Beijing in the fourth quarter of 2015： assessment of environmental benefits for red alerts

In recent years, Beijing has experienced severeair pollution which has caused widespread public concern.Compared to the same period in 2014, the first threequarters of 2015 exhibited significantly improved airquality. However, the air quality sharply declined in thefourth quarter of 2015, especially in November andDecember. During that time, Beijing issued the first redalert for severe air pollution in history. In total, 2 red alerts,3 orange alerts, 3 yellow alerts, and 3 blue alerts wereissued based on the adoption of relatively temporaryemergency control measures to mitigate air pollution. Thisstudy explored the reasons for these variations in airquality and assessed the effectiveness of emergency alertsin addressing severe air pollution. A synthetic analysis ofemission variations and meteorological conditions wasperformed to better understand these extreme air pollutionepisodes in the fourth quarter of 2015. The results showedthat compared to those in the same period in 2014, thedaily average emissions of air pollutants decreased in thefourth quarter of 2015. However, the emission levels ofprimary pollutants were still relatively high, which was themain intrinsic cause of haze episodes, and unfavorablemeteorological conditions represented important externalfactors. Emergency control measures for heavy airpollution were implemented during this red alert period,decreasing the emissions of primary air pollutants byapproximately 36% and the PMa.5 concentration by 11%-21%.

Removal of hydrophobic volatile organic compounds with sodium hypochlorite and surfactant in a co-current rotating packed bed

A co-current flow rotating packed bed was applied to remove volatile organic compounds（VOCs） by sodium hypochlorite（Na Cl O） and surfactant（sodium dodecyl benzene sulfonate,SDBS） from air stream. Xylene was used as a model VOC herein. The effect of p H,concentration of Na Cl O and SDBS solution, liquid flow rate, gas flow rate and rotational speed on xylene removal efficiency and overall mass transfer coefficient（KGa） were discussed. Then, a correlation for KGa of the co-current rotating packed bed was proposed by fitting the experimental data of KGa and independent variables of liquid/gas ratio,rotational speed, p H, Na Cl O concentration and treatment time, which was in good agreement with the experimental data（the deviation ≤ ± 30%）.

Determination of time-and size-dependent fine particle emission with varied oil heating in an experimental kitchen

Particulate matter（PM） from cooking has caused seriously indoor air pollutant and aroused risk to human health.It is urged to get deep knowledge of their spatial-temporal distribution of source emission characteristics,especially ultrafine particles（UFP ＆lt; 100 nm） and accumulation mode particles（AMP 100-555 nm）.Four commercial cooking oils are auto dipped water to simulate cooking fume under heating to 255℃ to investigate PM emission and decay features between 0.03 and 10 μm size dimension by electrical low pressure impactor（ELPI） without ventilation.Rapeseed and sunflower produced high PM_（2.5） around5.1 mg/m^3,in comparison with those of soybean and corn（5.87 and 4.55 mg/m^3,respectively）at peak emission time between 340 and 450 sec since heating oil,but with the same level of particle numbers 6-9 × 10~5/cm^3.Mean values of PM_（1.0）/PM_（2.5） and PM_（2.5）/PM_（10） at peak emission time are around 0.51-0.55 and 0.23-0.29.After 15 min naturally deposition,decay rates of PM_（1.0）,PM_（2.5） and PM_（10） are 13.3%-29.8%,20.1%-33.9%and 41.2%-54.7%,which manifest that PM_（1.0） is quite hard to decay than larger particles,PM_（2.5） and PM_（1.0）.The majority of the particle emission locates at 43 nm with the largest decay rate at 75%,and shifts to a larger size between137 and 555 nm after 15 min decay.The decay rates of the particles are sensitive to the oil type.

Recent progress of quantum dots for energy storage applications

The environmental problems of global warming and fossil fuel depletion are increasingly severe,and the demand for energy conversion and storage is increasing.Ecological issues such as global warming and fossil fuel depletion are increasingly stringent,increasing energy conversion and storage needs.The rapid development of clean energy,such as solar energy,wind energy and hydrogen energy,is expected to be the key to solve the energy problem.Several excellent literature works have highlighted quantum dots in supercapacitors,lithium-sulfur batteries,and photocatalytic hydrogen production.Here,we outline the latest achievements of quantum dots and their composites materials in those energy storage applications.Moreover,we rationally analyze the shortcomings of quantum dots in energy storage and conversion,and predict the future development trend,challenges,and opportunities of quantum dots research.

Two-dimensional quantum dots for biological applications

The two-dimensional quantum dots (2D-QDs) have been developed significantly in the past decades. The 2D-QDs could be used in bioimaging, biosensing, drug/gene delivery, and photodynamic/photothermal therapy. The potential applications in biology receive increasing attention, which makes them the novel and emerging candidates in biomaterial research fields. In this context, we discuss a variety of 2D-QDs with different physical and chemical properties. We focuse on the latest synthesis progress and recent applications in biotechnological, and biomedical applications of the 2D-QDs and we also evaluate the challenges and prospects in this field.