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Introduction and Objectives: Prostate apoptosis response protein-4 (PAR-4) is considered a tumor suppressor. However, the role of PAR-4 in hepatocellular carcinoma (HCC) has rarely been reported. The study explores the role of PAR-4 in the malignant behaviors of HCC cells. Materials and Methods: TCGA database was applied to analyze the expression of PAR-4 in HCC. Evaluated PAR-4 relationship with clinical parameters and prognosis by tissue microarray; expression of STAT3, p-STAT3, Src and Ras was detected by Western blotting or laser confocal microscopy. Cell scratch and flow cytometry assays were used to observe IL-6 regulation of the malignant behaviors of HCC cells. The tumorigenic potential of HCC cells in vivo was evaluated in a nude mouse tumor model. Results: Analysis indicated that the expression of PAR-4 in HCC tissues was significantly higher than that in normal liver tissues; and PAR-4 interacted with STAT3. KEGG analysis showed that PAR-4 plays a role in the Janus kinase (JAK)/STAT signaling pathway. The positive expression rate of PAR-4 in HCC tissues was significantly higher than that in adjacent tissues. Positive correlation between IL-6 and PAR-4 expression in the HCC tissues. Exogenous IL-6 significantly promoted the proliferation and migration of HCC cells and up-regulated the expression of PAR-4 and p-STAT3 in HCC cells. Interference of the expression of PAR-4 could reduce the malignant behaviors of HCC cells and inhibit tumorigenesis in a nude mouse tumor model. Conclusions: PAR-4 expression is positively correlated with HCC; PAR-4 promotes malignant behavior of HCC cells mediated by the IL-6/STAT3 signaling pathway.

Abstract Alpha-fetoprotein (AFP), a serum glycoprotein, is expressed during embryonic development and the pathogenesis of liver cancer. It serves as a clinical tumor marker, function as a carcinogen, immune suppressor, and transport vehicle; but the detailed AFP structural information has not yet been reported. In this study, we used single-particle cryo-electron microscopy(cryo-EM) to analyze the structure of the recombinant AFP obtained a 3.31 Å cryo-EM structure and built an atomic model of AFP. We observed and identified certain structural features of AFP, including N-glycosylation at Asn251, four natural fatty acids bound to distinct domains, and the coordination of metal ions by residues His22, His264, His268, and Asp280. Furthermore, we compared the structural similarities and differences between AFP and human serum albumin. The elucidation of AFP’s structural characteristics not only contributes to a deeper understanding of its functional mechanisms, but also provides a structural basis for developing AFP-based drug vehicles.

Background: Chronic pelvic pain (CPP) in women is a critical challenge. Due to the complex etiology and difficulties in diagnosis, it has a greatly negative impact on women's physical and mental health and the healthcare system. At present, there is still a lack of research on the related factors and predictive models of chronic pelvic pain in women. Our study aims to identify risk factors associated with chronic pelvic pain in women and develop a predictive nomogram specifically tailored to high-risk women with CPP. Materials and methods: From May to October 2022, trained interviewers conducted face-to-face questionnaire surveys and pelvic floor surface electromyography assessments on women from community hospitals in Nanjing. We constructed a multivariate logistic regression-based predictive model using CPP-related factors to assess the risk of chronic pelvic pain and create a predictive nomogram. Both internal and external validations were conducted, affirming the model's performance through assessments of discrimination, calibration, and practical applicability using area under the curve, calibration plots, and decision curve analysis. Results: 1108 women were recruited in total (survey response rate:1108/1200), with 169 (15.3 %) being diagnosed as chronic pelvic pain. Factors contributing to CPP included weight, dysmenorrhea, sexual dysfunction, urinary incontinence, a history of pelvic inflammatory disease, and the surface electromyography value of post-baseline rest. In both the training and validation sets, the nomogram exhibited strong discrimination abilities with areas under the curve of 0.85 (95 % CI: 0.81–0.88) and 0.85 (95 % CI: 0.79–0.92), respectively. The examination of the decision curve and calibration plot showed that this model fit well and would be useful in clinical settings. Conclusions: Weight, dysmenorrhea, sexual dysfunction, history of urinary incontinence and pelvic inflammatory disease, and surface electromyography value of post-baseline rest are independent predictors of chronic pelvic pain. The nomogram developed in this study serves as a valuable and straightforward tool for predicting chronic pelvic pain in women.

To resolve the congestion caused by imbalanced traffic at intersections, this paper establishes a model of the average delay deviation with the minimization of the average delay in the approach as the optimization objective. Then, the signal control scheme is further optimized based on the variable approach lanes setting. First, we investigate the threshold conditions for setting the VALs under different flows in a single approach direction. The results show that when the ratio of left-turn traffic exceeds the threshold range of 0.20~0.28, the function of the VALs needs to be changed from straight to left-turn. Then, based on the improved Webster’s formula, an optimal timing method that aims at minimizing the average vehicle delay, minimizing the queue length, and maximizing the capacity, is proposed. Finally, taking the actual Huangke intersection in the Hefei demonstration area as an example, three schemes are compared and analyzed in the case of a VAL at the intersection. The results show that under the cooperative optimization scheme proposed in this paper, the travel time and the efficiency of the intersection could be reduced by 18.7% and 9.9%, respectively, when compared with the original and Webster’s schemes.

Abstract Aim To evaluate a teaching experience in evidence‐based nursing learning through case‐based learning (CBL) and flipped learning (FL). Design Embedded mixed methods study. Methods In the first phase, a questionnaire on utility, satisfaction and perceived competency development is used to collect quantitative data, and the open question instrument is used to collect qualitative data. After the first phase, an in‐depth semi‐structured interview is used. Results Five themes are identified: the enhancement of learning content, knowledge integration and transfer, the development of teamwork competency, the didactic support of FL and the difficulties and challenges faced by students. Regarding utility, ‘combine theory and practice’ and ‘select the best evidence from what is found in the search’ have the highest values. The most developed skills are communication and critical thinking ability. Finally, most participants are satisfied. Conclusions The combination of CBL and FL is an innovative strategy for learning evidence‐based nursing courses. No Patient or Public Contribution.

Continuous monitoring of lower extremity muscles is necessary, as the muscles support many human daily activities, such as maintaining balance, standing, walking, running, and jumping. However, conventional electromyography and physiological cross-sectional area methods inherently encounter obstacles when acquiring precise and real-time data pertaining to human bodies, with a notable lack of consideration for user comfort. Benefitting from the fast development of various fabric-based sensors, this paper addresses these current issues by designing an integrated smart compression stocking system, which includes compression garments, fabric-embedded capacitive pressure sensors, an edge control unit, a user mobile application, and cloud backend. The pipeline architecture design and component selection are discussed in detail to illustrate a comprehensive user-centered STIMES design. Twelve healthy young individuals were recruited for clinical experiments to perform maximum voluntary isometric ankle plantarflexion contractions. All data were simultaneously collected through the integrated smart compression stocking system and a muscle force measurement system (Humac NORM, software version HUMAC2015). The obtained correlation coefficients above 0.92 indicated high linear relationships between the muscle torque and the proposed system readout. Two-way ANOVA analysis further stressed that different ankle angles (p = 0.055) had more important effects on the results than different subjects (p = 0.290). Hence, the integrated smart compression stocking system can be used to monitor the muscle force of the lower extremities in isometric mode.

Appropriate traffic cooperation at intersections plays a crucial part in modern intelligent transportation systems. To enhance traffic efficiency at intersections, this paper establishes a cooperative motion optimization strategy that adjusts the trajectories of autonomous vehicles (AVs) based on risk degree. Initially, AVs are presumed to select any exit lanes, thereby optimizing spatial resources. Trajectories are generated for each possible lane. Subsequently, a motion optimization algorithm predicated on risk degree is introduced, which takes into account the trajectories and motion states of AVs. The risk degree serves to prevent collisions between conflicting AVs. A cooperative motion optimization strategy is then formulated, incorporating car-following behavior, traffic signals, and conflict resolution as constraints. Specifically, the movement of all vehicles at the intersection is modified to achieve safer and more efficient traffic flow. The strategy is validated through a simulation using SUMO. The results indicate a 20.51% and 11.59% improvement in traffic efficiency in two typical scenarios when compared to a First-Come-First-Serve approach. Moreover, numerical experiments reveal significant enhancements in the stability of optimized AV acceleration.

Abnormal energy metabolism is one of the ten hallmarks of tumors, and tumor cell metabolism provides energy and a suitable microenvironment for tumorigenesis and metastasis. Tumor cells can consume large amounts of glucose and produce large amounts of lactate through glycolysis even in the presence of oxygen, a process called aerobic glycolysis, also known as the Warburg effect. Lactate is the end product of the aerobic glycolysis. Lactate dehydrogenase A (LDHA), which is highly expressed in cancer cells, promotes lactate production and transports lactate to the tumor microenvironment and is taken up by surrounding stromal cells under the action of monocarboxylate transporter 1/4 (MCT1/4), which in turn influences the immune response and enhances the invasion and metastasis of cancer cells. Therapeutic strategies targeting lactate metabolism have been intensively investigated, focusing on its metastasis-promoting properties and various target inhibitors; AZD3965, an MCT1 inhibitor, has entered phase I clinical trials, and the LDHA inhibitor N-hydroxyindole (NHI) has shown cancer therapeutic activity in pre-clinical studies. Interventions targeting lactate metabolism are emerging as a promising option for cancer therapy, with chemotherapy or radiotherapy combined with lactate-metabolism-targeted drugs adding to the effectiveness of cancer treatment. Based on current research, this article outlines the role of lactate metabolism in tumor metastasis and the potential value of inhibitors targeting lactate metabolism in cancer therapy.

Hepatocellular carcinoma (HCC) is a complex process that plays an important role in its progression. Abnormal glucose metabolism in HCC cells can meet the nutrients required for the occurrence and development of liver cancer, better adapt to changes in the surrounding microenvironment, and escape the attack of the immune system on the tumor. There is a close relationship between reprogramming of glucose metabolism and immune escape. This article reviews the current status and progress of glucose metabolism reprogramming in promoting immune escape in liver cancer, aiming to provide new strategies for clinical immunotherapy of liver cancer.

Abstract Aim This study aims to develop and validate a clinical nutrition risk screening tool to predict nutrition risk in home for the patients with gastric cancer after surgery at home so that high‐risk patients can be targeted for preventive nutrition care. Design The development of self‐screening tool for nutrition risk in patients with gastric cancer after gastrectomy (SNRSGC) through literature review, expert panel ratings and cognitive interview; the validation of SNRSGC is evaluated through prospective research on participants. Methods This research is divided into four parts: Step 1, Identification of a potential referred nutritional risk screening; Step 2, Item generation and scoring are selected through literature review methods to screen sensitive indicators which can reflect the nutritional characteristics of patients after gastric cancer surgery, establish the frame and update according to the latest guidelines; Step 3, Item reduction is determined by the rating of SNRSGC items by an expert panel and cognitive interview; Step 4, During the validation stage, we conducted research design based on the Consensus‐based Standards for the selection of health Measurement Instruments checklist to evaluate the validity, reliability, interpretability and acceptability of SNRSGC. Results SNRSGC is the first screening tool specifically to predict nutrition risk for stay‐at‐home postoperative patients with gastric cancer, which can help patients at home detect nutritional risks at home in time and guide patients to seek medical treatment as soon as possible to improve their nutritional status.

Abstract Aim This study aimed to evaluate the effect of abdominal massage (AM) on feeding intolerance (FI) in patients receiving enteral nutrition (EN). Design A systematic review and meta‐analysis. Methods We searched seven electronic databases to September 2021. STATA and RevMan were used to analyse the data. Results Eleven studies were included. The results revealed that AM could significantly reduce gastric residual volume and abdominal circumference difference, and reduce the incidence of gastric retention, vomiting, abdominal distention (all p

Alpha-fetoprotein(AFP) is a cancer biomarker for the diagnosis of hepatocellular carcinoma(HCC); however, its role in macrophage polarization and phagocytosis remains unclear. In the present study, we explored the correlation between AFP regulation of macrophage function and the possible regulatory mechanisms. Human mononuclear leukemia cells (THP-1) and monocytes from healthy donors were used to analyze the effect of AFP on the macrophages’ phenotype and phagocytosis. THP-1 cells and healthy human donor-derived monocytes were polarized into M0 macrophages induced by phorbol ester (PMA), and M0 macrophages were polarized into M1 macrophages induced by lipopolysaccharide(LPS) and interferon-γ(IFN-γ). Interleukin-4(IL-4) and interleukin-13(IL-13) were used to induce M0 macrophage polarization into M2 macrophages. Tumor-derived AFP(tAFP) stimulated M0 macrophage polarization into M2 macrophages and inhibited M1 macrophages to phagocytize HCC cells. The role of AFP in promoting macrophage polarization into M2 macrophages and inhibiting the M1 macrophages to phagocytize HCC cells may be involved in activating the PI3K/Akt signaling pathway. AFP could also enhanced the migration ability of macrophages and inhibited the apoptosis of HCC cells when co-cultured with M1-like macrophages. AFP is a pivotal cytokine that inhibits macrophages to phagocytize HCC cells.

Objective Explore the effect of GATA5 expression on Paclitaxel inhibiting growth of hepatocellular carcinoma (HCC) cells. Materials And Methods In the experimental study, HCC cell lines (HLE, Bel7402 and PLC/PRF/5) were treated with different concentrations of Paclitaxel (5-20 mg/ml) for 24 hours. HLE cells were transfected with GATA5-siRNA vector, while Bel7402 and PLC/PRF/5 cells were transfected with overexpressed GATA5 vector for 24 hours, followed by treatment of the cells with Paclitaxel (10 mg/ml) for 24 hours and subsequently 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay to detect growth of HCC cells. Soft agar cultured was used to analyze formation of colony. Apoptosis of HCC cells were detected by Flow cytometer. Migration of HCC cells was observed by trawell assays. Western blotting and laser confocal microscopy were utilized to detect expression and location of the proteins. Results Inhibiting expression of GATA5 reduced sensitivity of HLE cells to Paclitaxel, while overexpression of GATA5 increased sensitivity of Bel7402 cells and PLC/PRF/5 cells to Paclitaxel. Overexpression of GATA5 played a role in stimulating Paclitaxel to inhibit growth, colony formation and migration, as well as enhance apoptosis in HCC cells. Overexpression of GATA5 also promoted Paclitaxel to inhibit expression of reprogramming genes, such as Nanog, EpCAM, c-Myc and Sox2 in Bel7402 and PLC/PRF/5 cells. Inhibited expression of GATA5 led to enhancement of the expression of CD44 and CD133, in HLE cells. Overexpression of GATA5 was not only alone but also synergized with Paclitaxel to inhibit expression of CD44 and CD133 in Bel7402 or PLC/PRF/5 cells. Conclusion Overexpression of GATA5 played a role in enhancing Paclitaxel to inhibit the malignant behaviors of HCC cells. It was involved in suppressing expression of the reprogramming genes and stemness markers. Targeting GATA5 is an available strategy for applying paclitaxel to therapy of patients with HCC.

Filter bank multi-carrier (FBMC) using offset quadrature amplitude modulation (OQAM) has recently attracted increasing interests for the next-generation high-speed optical transmission systems, due to the salient FBMC modulation advantages in terms of high spectrum efficiency by completely removing the cyclic prefix. However, high peak-to-average power ratio (PAPR) still plays a key role of constraining the performance of FBMC systems. In this paper, we investigate a single sideband (SSB) pruned discrete Fourier transform (DFT)-spread FBMC for direct-detection (DD) passive optical network systems (PONs). It is demonstrated that the PAPR of the SSB pruned DFT-spread FBMC signal with the overlapping factor of 1.56 outperforms the conventional FBMC signal and the simple DFT-spread FBMC signal by ~2 dB and 1 dB at the complementary cumulative distribution function (CCDF) of 1 × 10-3, respectively. Finally, by using the pruned DFT-spread FBMC with low PAPR, the aggregate data rate of 50-Gbit/s can be achieved after 50-km single mode fiber (SMF) transmission below the 7% hard decision forward-error correction (HD-FEC) threshold in the DD PONs.

Hepatocellular carcinoma (HCC) is a common malignant tumor of which the occurrence and development, the tumorigenicity of HCC is involving in multistep and multifactor interactions. Interleukin-6 (IL-6), a multifunctional inflammatory cytokine, has increased expression in HCC patients and is closely related to the occurrence of HCC and prognosis. IL-6 plays a role by binding to the IL-6 receptor (IL-6R) and then triggering the Janus kinase (JAK) associated with the receptor, stimulating phosphorylation and activating signal transducer and activator of transcription 3 (STAT3) to initiate downstream signals, participating in the processes of anti-apoptosis, angiogenesis, proliferation, invasion, metastasis, and drug resistance of cancer cells. IL-6/STAT3 signal axes elicit an immunosuppressive in tumor microenvironment, it is important to therapy HCC by blocking the IL-6/STAT3 signaling pathway. Recent, some inhibitors of IL-6/STAT3 have been development, such as S31-201 or IL-6 neutralizing monoclonal antibody (IL-6 mAb), Madindoline A (Inhibits the dimerization of IL-6/IL-6R/gpl30 trimeric complexes), C188-9 and Curcumin (Inhibits STAT3 phosphorylation), etc. for treatment of cancers. Overall, consideration of the IL-6/STAT3 signaling pathway, and its role in the carcinogenesis and progression of HCC will contribute to the development of potential drugs for targeting treatment of liver cancer.

Abstract Background Recent evidences indicated that some local anaesthetic agents played a role in inhibiting the proliferation of cancer cells; Whether ropivacaine is able to promote apoptosis of hepatocellular carcinoma (HCC) cells is still unclear. The aim of this study was to investigate the effect of ropivacaine on the apoptosis of HCC cells. Methods In the present study, we treated the HCC cell lines, Bel7402 and HLE with ropivacaine. MTT, DAPI stain, trypan blue exclusion dye assay, flow cytometry, electron microscopy, computational simulation, laser confocal microscope, Western blotting, and enzyme activity analysis of caspase-3 were applied to detect the growth and apoptosis of HCC cells and to explore the role mechanism of ropivacaine. Results Ropivacaine was able to inhibit proliferation and promote apoptosis of HCC cells in a dose- and time-dependent manner. Ropivacaine also has a trait to inhibit the migration of HCC cells; ropivacaine damaged the mitochondria of HCC cells. The results also indicated that ropivacaine was able to interact with caspase-3, promote cytoplasmic caspase-3 migration into the nucleus, stimulate cleavage of caspase-3 and PARP-1, caspase-9 proteins, inhibit the expression of Bcl-2, promote expression of Apaf-1 and mitochondria release cytochrome C, and activate the activity of caspase-3. Conclusions Ropivacaine has a novel role in promoting apoptosis of HCC cells; The role mechanism of ropivacaine maybe involve in damaging the function of mitochondria and activating the caspase-3 signalling pathway in HCC cells. Our findings provide novel insights into the local anaesthetic agents in the therapy of HCC patients.

We propose and experimentally demonstrate a simple nonlinear equalizer based on functional-link neural network (FLNN). The nonlinear stochastic mapping enables FLNN to serve as a nonlinear network, so we construct an FLNN with the signals from the two polarizations and the mapped features as input to combat the fiber nonlinearity in coherent optical transmission systems. The FLNN can use the Moore-Penrose generalized inverse or the ridge regression to solve the weights, which can speed up the training process, and avoid the iterative and time-consuming training process that exist universally in most of the deep neural networks. We also extend the FLNN to the multi-channel transmissions. All of the received signals from different channels are stretched as the input and then we use a joint FLNN to extract features and equalize the nonlinear distortions. We conduct simulations and experiments to verify the proposed scheme. In the simulation and experiment, we transmit a 128 Gb/s polarization division multiplexed 16-QAM (PDM-16-QAM) signal over 1000-km and 600-km standard single mode fiber (SSMF), respectively. Both the simulation and experimental results show that the FLNN has similar performance as deep neural network (DNN), which can improve the transmission performance in the nonlinear region. Moreover, the FLNN can avoid the gradient dissipation and local minimum problems in DNN, which simplify the training process. We also extend the proposed scheme in a five-channel (5 ×160 Gb/s) multiplexed transmission system. In simulation, we use joint FLNN and joint DNN to compensate the nonlinear distortions, respectively. We find that the BERs of the five channels can be below 7% HD-FEC with nonlinear equalizer.

Alpha fetoprotein (AFP) plays a key role in stimulating the growth, metastasis and drug resistance of hepatocellular carcinoma (HCC). AFP is an important target molecule in the treatment of HCC. The application of AFP-derived peptides, AFP fragments and recombinant AFP (AFP-inhibiting fragments, AIFs) to inhibit the binding of AFP to intracellular proteins or its receptors is the basis of a new strategy for the treatment of HCC and other cancers. In addition, AIFs can be combined with drugs and delivery agents to target treatments to cancer. AIFs conjugated to anticancer drugs not only destroy cancer cells with these drugs but also activate immune cells to kill cancer cells. Furthermore, AIF delivery of drugs relieves immunosuppression and enhances chemotherapy effects. The synergism of immunotherapy and targeted chemotherapy is expected to play an important role in enhancing the treatment effect of patients with cancer. AIF delivery of drugs will be an available strategy for the targeted treatment of cancer in the future.

Alpha-fetoprotein (AFP) entrance into cancer cells is mediated by AFP receptors (AFPRs) and exerts malignant effects. Therefore, understanding the structure of AFPRs will facilitate the development of rational approaches for vaccine design, drug delivery, antagonizing immune suppression and diagnostic imaging to treat cancer effectively. Throughout the last three decades, the identification of universal receptors for AFP has failed due to their complex carbohydrate polymer structures. Here, we focused on the two types of binding proteins or receptors that may serve as AFPRs, namely, the A) mucin receptors family, and B) the scavenger family. We presented an informative review with detailed descriptions of the signal transduction, cross-talk, and interplay of various transcription factors which highlight the downstream events following AFP binding to mucin or scavenger receptors. We mainly explored the underlying mechanisms involved mucin or scavenger receptors that interact with AFP, provide more evidence to support these receptors as tumor AFPRs, and establish a theoretical basis for targeting therapy of cancer.

Mach-Zehnder (MZ) modulators are widely used in optical transmitters to generate high-speed optical signals. With electronic dispersion compensation (EDC), the driving signals to MZ modulators change from digital to analog, or continuous waveforms. Consequently, there is signal degradation from their sinusoidal transfer curves. In this paper, we theoretically and numerically investigate the signal degradation in optical transmitters using MZ modulators in the presence of EDC. We show that the temporal waveforms follow the Gaussian distribution when the EDC is large, and therefore, the modulation index needs to be optimized between the output SNR and the excess insertion loss of MZ modulators. With varying modulation index, we quantify the output SNR and excess insertion loss of optical IQ modulators that consist of two parallel MZ modulators. The calculations are also extended to the scenarios where the sinusoidal transfer curves are compensated for. All the analytical results are verified in a simulation of QPSK transmissions, and they are useful for finding an optimized modulation index for a tradeoff between the output SNR and excess insertion loss.

The study aimed to investigate the state of human papillomavirus (HPV) infection in patients with cervical cancer in the Uyghur population in China and to identify miRNA as biomarker for cervical cancer and HPV infection. We also performed genotyping to determine the variation in the types of HPV. Using microRNA (miRNA) microarray technology, differential miRNA expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined; the microarray results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) using 20 samples of both the tissues. The infection rate of HPV in patients with cervical cancer was 96.7% (29 of 30), and the main subtype identified was HPV16 (29 of 29). HPV16 integration assay demonstrated that the majority of infectious cases were of the integrated form (26 of 29). Analysis of 140 miRNAs demonstrated greater than two-fold change in miRNA expression in HPV-infected cervical cancer tissue as compared to that in uninfected cervical tissue. The qRT-PCR analysis verified that the expression of miR-15a-5p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-96, miR-106b-5p, and miR-3653 was higher, while the expression of miR-497-5p was lower in cancer tissues than in normal tissues. The results demonstrate significant changes in miRNA expression in cervical cancer tissues associated with HPV infection as compared to that in normal tissues. These molecular markers may be useful for an early diagnosis and prognosis of cervical cancer in specific human populations.

A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4) inhibitors. All compounds showed significant inhibitory activity against PAK4 (half-maximal inhibitory concentration IC50 < 1 μM). Among them, compounds 8d and 9c demonstrated the most potent inhibitory activity against PAK4 (IC50 = 0.060 μM and 0.068 μM, respectively). Furthermore, we observed that compounds 8d and 9c displayed potent antiproliferative activity against the A549 cell line and inhibited cell cycle distribution, migration, and invasion of this cell line. In addition, molecular docking analysis was performed to predict the possible binding mode of compound 8d. This series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity.

Nitrogen (N) is an essential nutrient for plant growth, and most plants absorb it as nitrate. AtNRG2 has been reported to play an important role in nitrate regulation. In this study, we investigated the functions of AtNRG2 family members of Arabidopsis thaliana and maize in nitrate signalling and metabolism. Our results showed that both AtNRG2.10 and AtNRG2.15 regulated nitrate signalling and metabolism. Overexpression of AtNRG2.11 (AtNRG2) could promote plant growth and improve nitrogen use efficiency (NUE). In addition, the maize genome harbors 23 ZmNRG2 members. We detected the expression of these genes treated with nitrate and the expression of four genes was strongly induced with ZmNRG2.7 having the highest levels. Overexpression of ZmNRG2.7 in the atnrg2 mutant could restore the defects of atnrg2, suggesting that ZmNRG2.7 is involved in nitrate signalling and metabolism. Moreover, the overexpression lines of ZmNRG2.7 showed increased biomass and NUE. These findings demonstrate that at least a part of NRG2 family genes in Arabidopsis and maize regulate nitrate signalling and provide a molecular basis for improving the NUE of crops. [ABSTRACT FROM AUTHOR]