Innovative strategies for photodynamic therapy against hypoxic tumor

Photodynamic therapy(PDT)is applied as a robust therapeutic option for tumor,which exhibits some advantages of unique selectivity and irreversible damage to tumor cells.Among which,photosensitizer(PS),appropriate laser irradiation and oxygen(O_(2))are three essential components for PDT,but the hypoxic tumor microenvironment(TME)restricts the O_(2) supply in tumor tissues.Even worse,tumor metastasis and drug resistance frequently happen under hypoxic condition,which further deteriorate the antitumor effect of PDT.To enhance the PDT efficiency,critical attention has been received by relieving tumor hypoxia,and innovative strategies on this topic continue to emerge.Traditionally,the O_(2) supplement strategy is considered as a direct and effective strategy to relieve TME,whereas it is confronted with great challenges for continuous O_(2) supply.Recently,O_(2)-independent PDT provides a brand new strategy to enhance the antitumor efficiency,which can avoid the influence of TME.In addition,PDT can synergize with other antitumor strategies,such as chemotherapy,immunotherapy,photothermal therapy(PTT)and starvation therapy,to remedy the inadequate PDT effect under hypoxia conditions.In this paper,we summarized the latest progresses in the development of innovative strategies to improve PDT efficacy against hypoxic tumor,which were classified into O_(2)-dependent PDT,O_(2)-independent PDT and synergistic therapy.Furthermore,the advantages and deficiencies of various strategies were also discussed to envisage the prospects and challenges in future study.

Exogenous SA Initiated Defense Response and Multi-signaling Pathway in Tetraploid Potato SD20

Salicylic acid(SA) is an important signaling substance that plays an important role in plant growth, development and disease resistance.In order to further understand the role of the SA pathway in potato disease resistance and identify SA signaling key genes, gene expression profiling of the late blight resistance genotype SD20 was performed under exogenous SA application. A total of 28 572 unigenes were assembled,of which 4 564 were differentially expressed. Analysis of differentially expressed genes(DEGs) showed that multiple signaling pathways such as SA, jasmonic acid, ethylene, abscisic acid, auxin, and brassinolide were involved in response to exogenous SA. Many plant defense signalrelated genes involved in protein serine/threonine kinase activity and plant-pathogen interaction, were significantly enriched. These were consistent with the interaction results of SD20 and Phytophthora infestans in our previous study, indicating that exogenous SA stimulated the resistance response and initiated a similar defense pathway compared to pathogen infection in SD20, which confirmed crosstalk of the SA signaling pathway with a pathogen-induced disease resistance signal pathway in plant. Moreover, transcriptome analysis revealed that ROS1 was positively regulated by SA in potato for the first time. SA-induced gene expression profiling provides insight into SA signaling and its mechanisms in disease defense systems.

Electro-chemo-mechanical design of polymer matrix in composited LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2) cathode endows solid-state batteries with superior performance

Nickel-rich LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811) cathode material has been widely concerned due to its high voltage,high specific capacity and excellent rate performance,which is considered as one of the most promising cathode materials for the next generation of high-energy-density solid-state lithium batteries.However,serious electro-chemo-mechanical degradation of Nickel-rich cathode during cycling,especially at a high voltage(over 4.5 V),constrains their large-scale application.Here,using the multiphysical simulation,highly-conductive polymer matrix with spontaneous stress-buffering effect was uncovered theoretically for reinforcing the electrochemical performance of composited NCM81 1 cathode through the visualization of uniform concentration distribution of Li-ion coupled with improved stress field inside NCM811 cathode.Thereupon,polyacrylonitrile(PAN) and soft polyvinylidene fluoride(PVDF) were selected as the polymer matrix to fabricate the composited NCM811 cathode(PVDFPAN@NCM811) for improving the electrochemical performance of the solid-state NMC811|Li full cells,which can maintain high capacity over 146.2 mA h g^(-1)after 200 cycles at a high voltage of 4.5 V.Suggestively,designing a multifunctional polymer matrix with high ionic conductivity and mechanical property can buffer the stress and maintain the integrity of the structure,which can be regarded as the door-opening avenue to realize the high electrochemical performance of Ni-rich cathode for solidstate batteries.

Automatic recognition of tweek atmospherics and plasma diagnostics in the lower ionosphere with the machine learning method

Tweek atmospherics are extremely low frequency and very low frequency pulse signals with frequency dispersion characteristics that originate from lightning discharges and that propagate in the Earth–ionosphere waveguide over long distances.In this study,we developed an automatic method to recognize tweek atmospherics and diagnose the lower ionosphere based on the machine learning method.The differences(automatic−manual)in each ionosphere parameter between the automatic method and the manual method were−0.07±2.73 km,0.03±0.92 cm^(−3),and 91±1,068 km for the ionospheric reflection height(h),equivalent electron densities at reflection heights(Ne),and propagation distance(d),respectively.Moreover,the automatic method is capable of recognizing higher harmonic tweek sferics.The evaluation results of the model suggest that the automatic method is a powerful tool for investigating the long-term variations in the lower ionosphere.

面向无线网–能源互联网双网融合系统的碳效用评估指标

随着国家“双碳战略”的稳步推进,无线通信领域缺少合理评估碳效用的相关指标,而传统的碳效用评估指标无法满足变化愈加剧烈的网络流量和网络部署、运维的特点.针对上述问题以及无线通信网–能源互联网双网融合的新趋势,本文提出了面向双网融合系统的集成相对碳效用指标(integrated relative carbon efficiency,IRCE).该指标不仅可以反映无线通信网络的容量和流量在时空上的动态变化,而且能够准确反映能源互联网的各个单元对双网融合系统的碳效用的影响.实验证明,所提出的集成相对碳效用指标不仅可以评估双网融合系统的碳效用水平,还可以反映能源供给侧不同的电能调度方式对碳效用的影响.

Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

Given that only a subset of patients with colorectal cancer(CRC)benefit from immune checkpoint therapy,efforts are ongoing to identify markers that predict immunotherapeutic response.Increasing evidence suggests that microbes influence the efficacy of cancer therapies.Fusobacterium nucleatum induces different immune responses in CRC with different microsatellite-instability(MSI)statuses.Here,we investigated the effect of F.nucleatum on anti-PD-L1 therapy in CRC.We found that high F.nucleatum levels correlate with improved therapeutic responses to PD-1 blockade in patients with CRC.Additionally,F.nucleatum enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged survival.Combining F.nucleatum supplementation with immunotherapy rescued the therapeutic effects of PD-L1 blockade.Furthermore,F.nucleatum induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma(IFN-γ)^(+)CD8^(+)tumor-infiltrating lymphocytes(TILs)during treatment with PD-L1 blockade,thereby augmenting tumor sensitivity to PD-L1 blockade.Finally,patient-derived organoid models demonstrated that increased F.nucleatum levels correlated with an improved therapeutic response to PD-L1 blockade.These findings suggest that F.nucleatum may modulate immune checkpoint therapy for CRC.

Correction To: Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/S41392-021-00795-x,published online 19 November 2021 In this article^(1) Qing Wei should have been denoted as a corresponding author along with Huanlong Qin,but was inadvertently removed during the production process.The original article has been corrected.

Gaussian Process Based Modeling and Control of Affine Systems with Control Saturation Constraints

Model-based methods require an accurate dynamic model to design the controller.However,the hydraulic parameters of nonlinear systems,complex friction,or actuator dynamics make it challenging to obtain accurate models.In this case,using the input-output data of the system to learn a dynamic model is an alternative approach.Therefore,we propose a dynamic model based on the Gaussian process(GP)to construct systems with control constraints.Since GP provides a measure of model confidence,it can deal with uncertainty.Unfortunately,most GP-based literature considers model uncertainty but does not consider the effect of constraints on inputs in closed-loop systems.An auxiliary system is developed to deal with the influence of the saturation constraints of input.Meanwhile,we relax the nonsingular assumption of the control coefficients to construct the controller.Some numerical results verify the rationality of the proposed approach and compare it with similar methods.