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Only a small proportion of patients with triple-negative breast cancer benefit from immune checkpoint inhibitor (ICI) targeting PD-1/PD-L1 signaling in combination with chemotherapy. Here, we discovered that therapeutic response to ICI plus paclitaxel was associated with subcellular redistribution of PD-L1. In our immunotherapy cohort of ICI in combination with nab-paclitaxel, tumor samples from responders showed significant distribution of PD-L1 at mitochondria, while non-responders showed increased accumulation of PD-L1 on tumor cell membrane instead of mitochondria. Our results also revealed that the distribution pattern of PD-L1 was regulated by an ATAD3A-PINK1 axis. Mechanistically, PINK1 recruited PD-L1 to mitochondria for degradation via a mitophagy pathway. Importantly, paclitaxel increased ATAD3A expression to disrupt proteostasis of PD-L1 by restraining PINK1-dependent mitophagy. Clinically, patients with tumors exhibiting high expression of ATAD3A detected before the treatment with ICI in combination with paclitaxel had markedly shorter progression-free survival compared with those with ATAD3A-low tumors. Preclinical results further demonstrated that targeting ATAD3A reset a favorable antitumor immune microenvironment and increased the efficacy of combination therapy of ICI plus paclitaxel. In summary, our results indicate that ATAD3A serves not only as a resistant factor for the combination therapy of ICI plus paclitaxel through preventing PD-L1 mitochondrial distribution, but also as a promising target for increasing the therapeutic responses to chemoimmunotherapy.

Calcyphosine (CAPS) was initially identified from the canine thyroid. It also exists in many types of tumor, but its expression and function in glioma remain unknown. Here we explored the clinical significance and the functional mechanisms of CAPS in glioma. We found that CAPS was highly expressed in glioma and high expression of CAPS was correlated with poor survival, in glioma patients and public databases. Cox regression analysis showed that CAPS was an independent prognostic factor for glioma patients. Knockdown of CAPS suppressed the proliferation, whereas overexpression of CAPS promoted the proliferation of glioma both in vitro and in vivo. CAPS regulated the G2/M phase transition of the cell cycle, but had no obvious effect on apoptosis. CAPS affected PLK1 phosphorylation through interaction with MYPT1. CAPS knockdown decreased p-MYPT1 at S507 and p-PLK1 at S210. Expression of MYPT1 S507 phosphomimic rescued PLK1 phosphorylation and the phenotype caused by CAPS knockdown. The PLK1 inhibitor volasertib enhanced the therapeutic effect of temozolomide in glioma. Our data suggest that CAPS promotes the proliferation of glioma by regulating the cell cycle and the PLK1 inhibitor volasertib might be a chemosensitizer of glioma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

The connection weights parameters play important roles in adjusting the performance of PID neural network (PIDNN) for complex control systems. However, how to obtain an optimal set of initial values of these connection weight parameters in a multivariable PIDNN called MPIDNN is still an open issue for system designers and engineers. This paper formulates this issue as a typical constrained optimization problem firstly by minimizing the cumulative sum of the product of exponential time and the system errors, and a real-time penalty function for overshoots of the system outputs, and then proposes an adaptive population extremal optimization-based MPIDNN method called PEO-MPIDNN for the optimal control issue of multivariable nonlinear control systems. The simulation results for two typical multivariable nonlinear control systems have demonstrated the superiority of the proposed PEO-MPIDNN to real-coded genetic algorithm (RCGA) and particle swarm optimization (PSO)-based MPIDNN, traditional MPIDNN with back propagation algorithm, and population extremal optimization-based multivariable PID control algorithm in terms of transient-state, steady-state, and robust control performance.

Background Leukemia is characterized by the presence of highly malignant tumors formed in the hematopoietic system. Artesunate (Art), a semi-synthetic derivative of artemisinin, is commonly used as an antimalarial drug and has been proven to possess anticancer potential. Methods In this study, the effect of Art on the proliferation and stemness of human acute promyelocyte leukemia HL-60 cells and acute myeloid leukemia KG1a cells was investigated. Flow cytometry, colony formation assay, the protein expressive levels of survivin, P21, cleaved caspase 3, Bax, Bcl-2, Ki67 were detected the effect of Art on HL-60 and KG1a cells proliferation and apoptosis. At the same time, cell sphere formation assay and the protein expressive levels of CD44, SOX2, ALDH1 and OCT4 were used to analyze the effects of Art on cancer stem cell-like property in vitro. The orthotopic xenograft mouse models were established by using KG1a cells in BALB/c athymic nude mice. Tumor weigh was detected. The protein levels of survivin and Ki67 were detected by immunohistochemistry assays. Results Art induced cell apoptosis and inhibited cell proliferation and stemness in a dose-dependent manner. In the meantime, the results exhibited that Art inhibited the growth and stemness of transplanted tumors via the suppression of the MEK/ERK and PI3K/Akt pathway. Conclusions Our present study provides new insights into the mechanisms of Art's anticancer potential in leukemia.

How to design a set of optimal distributed load frequency controllers for a multi-area interconnected power system is an important but still challenging issue in the field of modern electric power systems. This paper presents an adaptive population extremal optimization-based extended distributed model predictive load frequency control method called PEO-EDMPC for a multi-area interconnected power system. The key idea behind the proposed method is formulating the dynamic load frequency control issue of each area power system as an extended distributed discrete-time state-space model based on an extended state vector, obtaining a distributed dynamic extended predictive model, and rolling optimization of real-time control output signal by adopting an adaptive population extremal optimization algorithm, where the fitness is evaluated by the weighted sum of square predicted errors and square future control values. The superiority of the proposed PEO-EDMPC method to a traditional distributed model predictive control method, a population extremal optimization-based distributed proportional-integral control algorithm and a traditional distributed integral control method is demonstrated by the simulation studies on two-area and three-area interconnected power systems in cases of normal, perturbed system parameters and dynamical load disturbances.

The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1). Consistently, the tamoxifen-induced stemness and metastasis can be attenuated by either ALDH1 inhibitors or a specific ERα36 antibody. Thus, tamoxifen acts as an agonist on ERα36 in breast cancer cells, which accounts for hormone therapy resistance and metastasis of breast cancer. Our study not only reveals ERα36 as a stratifying marker for endocrine therapy but also provides a promising therapeutic avenue for tamoxifen-resistant breast cancer.

How to design an optimal mixed H 2 /H ∞ robust FID controller for a complex control system is of great practical importance, but it is still an open issue. From the perspective of evolutionary algorithm, this paper formulates this issue firstly as a typical constrained optimization problem by minimizing a weighted objective function consisting of the robust stability performance, disturbance attenuation performance and tracking error, and then presents a novel a novel optimal design method of mixed H 2 /H ∞ robust FID controllers based on a constrained evolutionary algorithm called CEO-DE by combining constrained extremal optimization and differential evolution. The simulation results on two typical multi-variable control systems have demonstrated the proposed CEO-DE based design method performs better than some reported popular methods such as intelligent genetic algorithm and multi-objective particle swarm optimization.

How to design an effective and efficient load-frequency controller (LFC) for a multi-area interconnected power system to improve its power quality is a challenging issue. In order to deal with this issue, this paper presents a novel distributed fractional-order PID (DFOPID) control method for the load-frequency control of each area by using an adaptive population-based extremal optimization (APEO) algorithm. The basic idea behind the proposed method is formulating the optimal design issue of DFOPID controller as a typical constrained optimization problem by minimizing the weighted sum of area control errors and the control signal subjecting to some pre-specified tolerances firstly, and then solving this problem by using APEO algorithm. The simulation results on a two-area interconnected power system with matched and mismatched system parameters have shown that the proposed method is superior to reported genetic algorithm, particle swarm optimization and chaotic NSGA-II algorithm based fractional-order LFC methods in terms of dynamic response and robustness.

Fractional order proportional-integral-derivative(FOPID) controllers have attracted increasing attentions recently due to their better control performance than the traditional integer-order proportional-integral-derivative (PID) controllers. However, there are only few studies concerning the fractional order control of microgrids based on evolutionary algorithms. From the perspective of multi-objective optimization, this paper presents an effective FOPID based frequency controller design method called MOEO-FOPID for an islanded microgrid by using a Multi-objective extremal optimization (MOEO) algorithm to minimize frequency deviation and controller output signal simultaneously in order to improve finally the efficient operation of distributed generations and energy storage devices. Its superiority to nondominated sorting genetic algorithm-II (NSGA-II) based FOPID/PID controllers and other recently reported single-objective evolutionary algorithms such as Kriging-based surrogate modeling and real-coded population extremal optimization-based FOPID controllers is demonstrated by the simulation studies on a typical islanded microgrid in terms of the control performance including frequency deviation, deficit grid power, controller output signal and robustness.

Fractional order control theories have attracted increasing attentions recently due to their better control performance than traditional integer-order controllers, but there are few research works concerning their applications of power systems and power converters. This paper presents a novel binary-coded extremal optimization (BCEO) based fractional-order frequency control method for an islanded microgrid. The basic idea behind the proposed method is using an optimal fractional-order PID (FOPID) controller optimized by a simple but efficiency BCEO algorithm for the frequency control of an islanded microgrid. The superiority of the proposed BCEO-FOPID method to other reported binary-coded genetic algorithm based FOPID/PID, particle swarm optimization based fuzzy FOPID and BCEO based PID algorithms is demonstrated by the simulation results on a typical islanded microgrid.

To explore the differences of CD146 expression in adult and children's acute B cell lymphoblastic leukemia(B-ALL), and its relation with clinical features, molecular biological and cytogenctic claracteristics.The expression of CD146 in bone marrow samples from adult and children's B-ALL patients were detected by flow cytometry (FCM) and the relation of CD146 abnormal high expression with the patients' clinical features, molecular biological and cytogenetical characteristics, as well as other antigens were analyzed.The abnormal high expression rates of CD146 in adult and children's B-ALL patients were 29.17% and 9.09% respectively, showing that the expression rate of CD146 in adult patients was higher than that in children's patients(P0.05). In adult B-ALL, CD146 was positively related with CD64 and CD117, while in children's B-ALL CD146 was positively related with CD71 and CD58 (P0.05). After 1 course of standardized chemotherapy, the complete remission rates in adult and children's B-ALL patients with abnormal high expression of CD146 both were low as compared with adult and children's B-ALL without abnormal high expression of CD146 (P0.05).The expression rate of CD146 in adult B-ALL is higher than that in children's B-ALL. The CD146 positively relates with poor prognostic antigens, the CD146 may be one poor prognosis marker.

This paper studies the accurate prediction problem of VRLA battery state of charge (SOC) and the remaining capability of the battery, after the comprehensive analysis of the various elements which affect the battery state of charge, we put forward a battery degradation test model based on GA - WNN, and carries on the verification test, in the meantime, we also make it contrast with other algorithms. The results of test show that the model of WNN Optimized by GA has shorter training time and high prediction accuracy, it can predict the battery remaining power more accurately.

A numerical study with FLUENT software has been carried out as to air performance in the slope solar energy power plant. The velocity field, temperature and pressure fields in the solar chimney, and the simulated result were compared with the simulated result of traditional solar chimney power generating equipment. The simulation results show that distribution of the temperature field and the velocity field in slope solar energy power plant and traditional solar chimney power generating equipment. In the case of the same height, the velocity of traditional is slightly larger than the slope style's, but there is little difference. In order to achieve the same power generation effect, the overall height of slope style is more than the traditional style, but the vertical chimney height of traditional style is greater than the slope style. The cost of construction of vertical chimney is expensive, and many problems have been considered, like radix saposhnikoviae and earthquake prevention, the heat collector also need to be cleaned on time. The slope style can take full advantage of land, the height of vertical chimney will be reduced, so the construction of the chimney will be relatively easy. Rainwater can clean the heat collector when it runs down from it. All things considered. The slope solar energy power plant has more development prospects.

At present, test interpretation technology is still based on the rule and theory during 1960s-1980s, which wasn’t be developed and improved further in view of the new problems in field. The field practice and theory comparison have shown that these basic theory and interpretation model diverges obviously appropriate category, and have the singlet, unilateral problem of considered element, which can’t adapt to the quantification description of complex filtrate in porous medium. The basic theory and mathematic model of tracer test interpretation need to develop further, and interpretation means needs to improve corroboratively. From the point of numerical mathematics, the independent variables in reservoirs were found out and the objective function was constructed. Making use of improved real-number-style inheritance-arithmetic, the unitary parameters inversion and interpretation were accomplished in inter well tracer test.

Assisted colonization of endangered species to locations outside their native ranges in response to projected climate change has emerged as a potential, but highly controversial conservation tool. The debate has been largely philosophical and hypothetical as little biological data exist in the literature. In 2006, nearly 1000 endangered wild orchid plants belonging to 29 species were translocated to higher elevations in subtropical southwestern China in response to inundation threats from a hydropower project. We took advantage of this upward translocation to address one of the main biological concerns associated with assisted colonization, i.e. whether the target endangered species can survive in the novel environment that is projected to be suitable for them, sometime in the future. We assessed the impacts of two extreme weather events, translocation shock and herbivory, on survival of 20 of these species and 462 individuals that were translocated beyond their current range vs. within that range. A cold spell in 2008 on average caused 10% mortality, less than the mortality rate from herbivores. However, the cold spell was the only force that extirpated an out-of-range population. No mortality resulted from a drought event in 2010. The 5-year survival percentages were not different between low and wide elevation species (69.3% mean ± 36.3% standard deviation vs. 67.3% ± 30.9%). Orchids represent 10% of flowering plant diversity and are among the most endangered group of organisms due to a combination of their often specialized ecological requirements, habitat destruction, and overexploitation. The demonstrated ability to survive extreme environmental challenges indicates that assisted colonization may be a viable conservation tool for the many endangered orchids worldwide due to climate change and/or other reasons.

Physical simulation experiments were made to research on the stress sensitivity on physical property of low permeability reservoir rocks. The experimental results shown that effective pressure had good exponential relationship with reservoir permeability. Combining with materaial balance method, reservoir engineering and rational deducation was made to reserach on water-flooding timing of low permeability reservoir development. Several production targets were obtained by these method, such as formation pressure, water and oil production, water cut and so on. The results shown that advanced water-flooding was very important in low permeability reservoir development to reduce the bad impact of stress sensitivity on formation permeability and maintain formation pressure.

The school-enterprise cooperation is an important way to train highly-skilled personnel, improve independent innovation capacity. This paper based on the research of the current school-enterprise cooperation mode and its obstacles, analysing the operation mechanism of this mode, and thus proposing a rational choice of sustainable operational mechanism for building a school-enterprise cooperation mode of training high-skilled talents.

Post-earthquake restoration and reconstruction work is a huge social project, the disposal of post-earthquake property is a complex and urgent issue. At present, the research on this area is still in a preliminary stage. By means of comparative studying on domestic and international documents, this paper classified the post-earthquake property, through the case study of Beichuan and field test of local post-earthquake property disposal situation, analyses the problems existing in the current mechanism, puts forward a scientific and rational suggestions, expecting to solve the problems and conflicts, promoting social stability and development in earthquake stricken area.

BioWin software and two sensitivity analysis methods were used to simulate the Denitrification Biological Filter (DNBF) + Biological Aerated Filter (BAF) process in Yuandang Wastewater Treatment Plant. Based on the BioWin model of DNBF + BAF process, the operation data of September 2013 were used for sensitivity analysis and model calibration, and the operation data of October 2013 were used for model validation. The results indicated that the calibrated model could accurately simulate practical DNBF + BAF processes, and the most sensitive parameters were the parameters related to biofilm, OHOs and aeration. After the validation and calibration of model, it was used for process optimization with simulating operation results under different conditions. The results showed that, the best operation condition for discharge standard B was: reflux ratio = 50%, ceasing methanol addition, influent C/N = 4.43; while the best operation condition for discharge standard A was: reflux ratio = 50%, influent COD = 155 mg x L(-1) after methanol addition, influent C/N = 5.10.

To investigate the clinical effects of epidural clonidine pretreatment in epidural patient-controlled analgesia (PCA) using sufentanil combined with levobupivacaine.Sixty patients undergoing abdominal hysterectomy of ASA status I-II were randomly divided into 3 equal groups: C2 group was pretreated with epidural clonidine 2 microg/kg at the L2-3 interspace, 15 min later, epidural anesthesia was performed with 0.5% levobupivacaine, and then 0. 4 microg/ml combined with levobupivacaine 2 mg/ml was given for postoperative epidural patient-controlled analgesia. C4 group was pretreated with epidural clonidine 4 microg/kg, and C0 group was pretreated with normal saline. The analgesic effect, PCA drug dosage, adverse reaction, and visual analog scale (VAS) score were recorded.Anesthesia was clinically satisfactory in all patients. The rate of atropine use of the C4 group was 30%, significantly higher than those of the C2 group (15% ) and C0 group (5%, both P0.05). The rate of VASor = 3 at rest 24 h postoperatively of the C2 and C4 groups were 88% and 93% respectively, both significantly higher than that of the C0 group (75%, P0.01 and P0.01). The rate of VASor = 3 while coughing 24 h postoperatively of the C2 and C4 groups were 61% and 79% respectively, both significantly higher than that of the C0 group (48%). The dosages of PCA drug of the C2 and C4 groups were significantly lower than that of the C0 group by 11.8% and 22.8% respectively (both P0.05). The dosage of PCA drug 0-4 h after operation of the C2 was significantly higher than that of the C4 group. The sedative degree of the C4 group was higher than that of the C0 group. The rate of postoperative vomiting of the C0 group was 40%, significantly higher than that of the C4 group (10%, P0.05).Epidural clonidine 2-4 microg/kg pretreatment improves the clinical effects of epidural PCA using sufentanil combined with levobupivacaine.