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Abstract Triple-negative breast cancer (TNBC) is the most malignant molecular subtype of breast cancer and is characterized by aggressiveness, high mortality, significant heterogeneity, and poor prognosis. AMPK plays a critical role in maintaining the cellular energy balance, and its inactivation is associated with malignant breast cancer. Here, we identified the pharmacological mechanism of the 1,4-naphthoquinone derivative ZSW-4B. MTT, colony formation, and nude mouse xenograft tumour models demonstrated that ZSW-4B selectively inhibits the proliferation of TNBC cells both in vitro and in vivo. Flow cytometry and Western blot analysis revealed that ZSW-4B induces apoptosis in TNBC cells. Phosphoproteomic analysis revealed activation of the AMPK signalling pathway by ZSW-4B. Additionally, the application of the CRISPR-Cas9 system to genetically knockout AMPK in TNBC cell lines was demonstrated to reverse the antitumour effects elicited by ZSW-4B both in vitro and in vivo. In summary, ZSW-4B inhibits TNBC by inducing cellular apoptosis through the activation of AMPK.

Abstract Background Temperature is a crucial environmental determinant for the vitality and development of teleost fish, yet the underlying mechanisms by which they sense temperature fluctuations remain largely unexplored. Transient receptor potential (TRP) proteins, renowned for their involvement in temperature sensing, have not been characterized in teleost fish, especially regarding their temperature-sensing capabilities. Results In this study, a genome-wide analysis was conducted, identifying a total of 28 TRP genes in the mandarin fish Siniperca chuatsi. These genes were categorized into the families of TRPA, TRPC, TRPP, TRPM, TRPML, and TRPV. Despite notable variations in conserved motifs across different subfamilies, TRP family members shared common structural features, including ankyrin repeats and the TRP domain. Tissue expression analysis showed that each of these TRP genes exhibited a unique expression pattern. Furthermore, examination of the tissue expression patterns of ten selected TRP genes following exposure to both high and low temperature stress indicated the expression of TRP genes were responsive to temperatures changes. Moreover, the expression profiles of TRP genes in response to mandarin fish virus infections showed significant upregulation for most genes after Siniperca chuatsi rhabdovirus, mandarin fish iridovirus and infectious spleen and kidney necrosis virus infection. Conclusions This study characterized the TRP family genes in mandarin fish genome-wide, and explored their expression patterns in response to temperature stress and virus infections. Our work will enhance the overall understanding of fish TRP channels and their possible functions.

Abstract Argininosuccinate synthase (ASS1), a critical enzyme in the urea cycle, acts as a tumor suppressor in many cancers. To date, the anticancer mechanism of ASS1 has not been fully elucidated. Here, we found that phosphoglycerate dehydrogenase (PHGDH), a key rate-limiting enzyme in serine synthesis, is a pivotal protein that interacts with ASS1. Our results showed that ASS1 directly binds to PHGDH and promotes its ubiquitination-mediated degradation to inhibit serine synthesis, consequently suppressing tumorigenesis. Importantly, the tumor suppressive effects of ASS1 were strongly abrogated by PHGDH knockout. In addition, ASS1 knockout and knockdown partially rescued cell proliferation when serine and glycine were depleted, while the inhibitory effect of ASS1 overexpression on cell proliferation was restored by the addition of serine and glycine. These findings unveil a novel role of ASS1 and suggest that the ASS1/PHGDH serine synthesis pathway is a promising target for cancer therapy.

ObjectiveExisting studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases.MethodsWe utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action.ResultsThe MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease.ConclusionsFrom predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.

Since the existing software defined network (SDN) security prediction methods do not consider the attack cost and the impact of controller vulnerabilities on SDN security, a Bayesian attack graph-based algorithm to assessing SDN intrusion intent was proposed.The PageRank algorithm was used to obtain the criticality of the device, and combining with the vulnerability value, attack cost, attack benefit and attack preference, an attack graph was constructed, and a risk assessment model was established to predict the intrusion path.Through experimental comparison, it is obvious that the proposed model can more accurately predict the intrusion path, effectively ensure the accuracy of security prediction, and provide a basis for SDN defense.

Because of the difference between satellite-ground link and ground propagation loss characteristics, the spectrum effi ciency index of satellite communication system is far lower than that of terrestrial cellular system in the same period.It is of utility to improve spectral effi ciency by realizing effi cient space division multiplexing with multi-beam antennas.The adaptive beamforming and doppler frequency off set compensation scheme in the LEO multi-beam satellite communication scenario was studied.Firstly, a low-complexity hybrid beamforming scheme was designed.Then, aim at the doppler frequency shifts were diff erent between beams due to their pitch angles, a doppler frequency off set pre-compensation scheme for multi-beam systems was proposed.Finally, the eff ectiveness of the algorithm was verifi ed by MATLAB simulation analysis.

Orbit angular momentum (OAM) has been considered a new dimension for improving channel capacity in recent years. In this paper, a millimeter-wave broadband multi-mode waveguide traveling-wave antenna with OAM is proposed by innovatively utilizing the transmitted electromagnetic waves (EMWs) characteristic of substrate-integrated gap waveguides (SIGWs) to introduce phase delay, resulting in coupling to the radiate units with a phase jump. Nine “L”-shaped slot radiate elements are cut in a circular order at a certain angle on the SIGW to generate spin angular momentum (SAM) and OAM. To generate more OAM modes and match the antenna, four “Π”-shaped slot radiate units with a 90° relationship to each other are designed in this circular array. The simulation results show that the antenna operates at 28 GHz, with a −10 dB fractional bandwidth (FBW) = 35.7%, ranging from 25.50 to 35.85 GHz and a VSWR ≤ 1.5 dB from 28.60 to 32.0 GHz and 28.60 to 32.0 GHz. The antenna radiates a linear polarization (LP) mode with a gain of 9.3 dBi at 34.0~37.2 GHz, a l = 2 SAM–OAM (i.e., circular polarization OAM (CP–OAM)) mode with 8.04 dBi at 25.90~28.08 GHz, a l = 1 and l = 2 hybrid OAM mode with 5.7 dBi at 28.08~29.67 GHz, a SAM (i.e., left/right hand circular polarization (L/RHCP) mode with 4.6 dBi at 29.67~30.41 GHz, and a LP mode at 30.41~35.85 GHz. In addition, the waveguide transmits energy with a bandwidth ranging from 26.10 to 38.46 GHz. Within the in-band, only a quasi-TEM mode is transmitted with an energy transmission loss |S21| ≤ 2 dB.

A meta-surface-based arbitrary bandwidth filter realization method for terahertz (THz) future communications is presented. The approach involves integrating a meta-surface-based bandstop filter into an ultra-wideband (UWB) bandpass filter and adjusting the operating frequency range of the meta-surface bandstop filter to realize the design of arbitrary bandwidth filters. It effectively addresses the complexity of designing traditional arbitrary bandwidth filters and the challenges in achieving impedance matching. To underscore its practicality, the paper employs silicon substrate integrated gap waveguide (SSIGW) and this method to craft a THz filter. To begin, design equations for electromagnetic band gap (EBG) structures were developed in accordance with the requirements of through-silicon via (TSV) and applied to the design of the SSIGW. Subsequently, this article employs equivalent transmission line models and equivalent circuits to conduct theoretical analyses for both the UWB passband and the meta-surface stopband portions. The proposed THz filter boasts a center frequency of 0.151 THz, a relative bandwidth of 6.9%, insertion loss below 0.68 dB, and stopbands exceeding 20 GHz in both upper and lower ranges. The in-band group delay is 0.119 ± 0.048 ns. Compared to reported THz filters, the SSIGW filter boasts advantages such as low loss and minimal delay, making it even more suitable for future wireless communication.

In this paper, we study the fixed-time formation (FixF) control problem for the nonlinear second-order multi-agent systems (MASs) with directed graph, where all agents are subject to communication disturbances. To overcome the bounded disturbance of communication and to guarantee the realization of predesignated formation within a fixed-time, a suitable FixF control protocol based on the backstepping method is proposed. Furthermore, to eliminate the dependence of the control parameters on global information, a new adaptive FixF control protocol is provided to combine with some mild conditions of control gain such that the formation with acceptable bounded error of MASs can be achieved within a fixed-time. Finally, the theoretical results are verified by two simulation examples, one of the simulation examples is that we set the desired formation as a regular octagon and the desired formation motion trajectory as a circle, the results show that all agents can form formation motion within a fixed-time.

Arginine addiction induced by argininosuccinate synthase (ASSN1) deficiency has been exploited to treat ASS1-deficient cancers. Here, the authors show an alternative therapeutic approach where ASS1 activity is increased by the pesticide spinosyn A and is shown to inhibit breast cancer cell proliferation.

Aiming at the problem of ignoring the impact of attack cost and intrusion intention on network security in the current network risk assessment model,in order to accurately assess the target network risk,a method of network intrusion intention analysis based on Bayesian attack graph was proposed.Based on the atomic attack probability calculated by vulnerability value,attack cost and attack benefit,the static risk assessment model was established in combination with the quantitative attack graph of Bayesian belief network,and the dynamic update model of intrusion intention was used to realize the dynamic assessment of network risk,which provided the basis for the dynamic defense measures of attack surface.Experiments show that the model is not only effective in evaluating the overall security of the network,but also feasible in predicting attack paths.

Summary: Aquaculture provides important food, nutrition, and income sources for humans. However, aquaculture industry is seriously threatened by viral diseases. Infectious spleen and kidney necrosis virus (ISKNV) disease causes high mortality and economic losses to the fish culture industry in Asia and has been listed as a certifiable disease by the International Epizootic Office. Vaccine development is urgent to control this disease. Here, a gene-deleted live attenuated candidate vaccine (ΔORF022L) against ISKNV with low pathogenicity and high protection was developed. ΔORF022L replicated well in mandarin fish fry-1 cells and showed similar structure with wild-type ISKNV. However, the pathogenicity was significantly lower as 98% of the mandarin fish infected with ΔORF022L survived, whereas all those infected with wild-type ISKNV died. Of importance, 100% of the ΔORF022L-infected fish survived the ISKNV challenge. ΔORF022L induced anti-ISKNV specific antibody response and upregulation of immune-related genes. This work could be beneficial to the control of fish diseases.

To ensure that the system could still provide normal service for legitimate users when the LAN being invaded,a finite automaton intrusion tolerance model was designed.Based on Markov’s theory,the state transformation relationship of the service provided by the system by establishing the state transition probability matrix was described,quantified the transition state and found the key nodes in the system.The maintenance of key nodes could enhance the tolerance of the system and improve the reliability of the service.Experimental comparison shows that this model not only has strong intrusion tolerance,but also has obvious advantages in the integrity of the security system when it is invaded.

With the rapid development of sensor technology for automated driving applications, the fusion, analysis, and application of multimodal data have become the main focus of different scenarios, especially in the development of mobile edge computing technology that provides more efficient algorithms for realizing the various application scenarios. In the present paper, the vehicle status and operation data were acquired by vehicle-borne and roadside units of electronic registration identification of motor vehicles. In addition, a motion model and an identification system for the single-vehicle lane-change process were established by mobile edge computing and self-organizing feature mapping. Two scenarios were modeled and tested: lane change with no vehicles in the target lane and lane change with vehicles in the target lane. It was found that the proposed method successfully identified the stochastic parameters in the process of driving trajectory simulation, and the standard deviation between simulation and the measured results obeyed a normal distribution. The proposed methods can provide significant practical information for improving the data processing efficiency in automated driving applications, for solving single-vehicle lane-change applications, and for promoting the formation of a closed loop from sensing to service.

In the development of technology for smart cities, the installation and deployment of electronic motor vehicle registration identification have attracted great attention in terms of smart transportation in recent years. Vehicle velocity measurement is one of the fundamental data collection efforts for motor vehicles. The velocity detection using electronic registration identification of motor vehicles is constrained by the detection algorithm, the material of the automobile windshield, the placement of the decals, the installation method of the signal reader, and the angle of the antenna. The software and hardware for electronic motor vehicle registration identification produced in the standard manner cannot meet the accuracy of velocity detection for all scenarios. Based on the actual application requirements, we propose a calibration method for the numerical output of the automobile velocity detector based on edge computing of the optimized multiple reader/writer velocity values and based on a particle swarm-optimized radial basis function (RBF) neural network. The proposed method was tested on a two-way eight-lane road, and the test results showed that it can effectively improve the accuracy of velocity detection using electronic registration identification of motor vehicles. Compared with the actual velocity, 87.12% of all the data samples had an error less than 5%, and 91.76% of the data samples for vehicles in the center lane had an error less than 5%. By calibrating the electronic vehicle velocity based on the registration identification, the accuracy of velocity detection in different application environments can be improved. Moreover, the method can establish an accurate foundation for application in traffic flow management, environmental protection, traffic congestion fee collection, and special vehicle traffic management.

Ginseng (Panax ginseng C.A. Mey.) is a precious Chinese traditional medicine, for which ginsenosides are the most important medicinal ingredients. Cytochrome P450 enzymes (CYP450) and their primary redox molecular companion NADPH cytochrome P450 reductase (CPR) play a key role in ginsenoside biosynthesis pathway. However, systematic studies of CPR genes in ginseng have not been reported. Numerous studies on ginsenoside synthesis biology still use Arabidopsis CPR (AtCPR1) as a reductase. In this study, we isolated two CPR genes (PgCPR1, PgCPR2) from ginseng adventitious roots. Phylogenetic tree analysis showed that both PgCPR1 and PgCPR2 are grouped in classⅡ of dicotyledonous CPR. Enzyme experiments showed that recombinant proteins PgCPR1, PgCPR2 and AtCPR1 can reduce cytochrome c and ferricyanide with NADPH as the electron donor, and PgCPR1 had the highest enzymatic activities. Quantitative real-time PCR analysis showed that PgCPR1 and PgCPR2 transcripts were detected in all examined tissues of Panax ginseng and both showed higher expression in stem and main root. Expression levels of the PgCPR1 and PgCPR2s were both induced after a methyl jasmonate (MeJA) treatment and its pattern matched with ginsenoside accumulation. The present investigation suggested PgCPR1 and PgCPR2 are associated with the biosynthesis of ginsenoside. This report will assist in future CPR family studies and ultimately improving ginsenoside production through transgenic engineering and synthetic biology.

Fatty acid synthase (FASN) is a key enzyme in the synthesis of palmitate, the precursor of major nutritional, energetic, and signaling lipids. FASN expression is upregulated in many human cancers and appears to be important for cancer cell survival. Overexpression of FASN has also been found to associate with poor prognosis and higher risk of recurrence of human cancers. Indeed, elevated FASN expression has been shown to contribute to drug resistance. However, the mechanism of FASN-mediated drug resistance is currently unknown. In this study, we show that FASN overexpression causes resistance to multiple anticancer drugs via inhibiting drug-induced ceramide production, caspase 8 activation, and apoptosis. We also show that FASN overexpression suppresses tumor necrosis factor-α production and nuclear factor-κB activation as well as drug-induced activation of neutral sphingomyelinase. Thus, TNF-α may play an important role in mediating FASN function in drug resistance.