Data association based on target signal classification information

In most of the passive tracking systems, only the target kinematical information is used in the measurement-to-track association, which results in error tracking in a multitarget environment, where the targets are too close to each other. To enhance the tracking accuracy, the target signal classification information （TSCI） should be used to improve the data association. The TSCI is integrated in the data association process using the JPDA （joint probabilistic data association）. The use of the TSCI in the data association can improve discrimination by yielding a purer track and preserving continuity. To verify the validity of the application of TSCI, two simulation experiments are done on an air target-tracing problem, that is, one using the TSCI and the other not using the TSCI. The final comparison shows that the use of the TSCI can effectively improve tracking accuracy.

Ground moving target signal model and power calculation in forward scattering micro radar

Forward scattering micro radar is used for situation awareness; its operational range is relatively short because of the battery power and local horizon, the free space propagation model is not appropriate. The ground moving targets, such as humans, cars and tanks, have only comparable size with the transmitted signal wavelength; the point target model and the linear change of observation angle are not applicable. In this paper, the signal model of ground moving target is developed based on the case of forward scattering micro radar, considering the two-ray propagation model and area target model, and nonlinear change of observation angle as well as high order phase error. Furthermore, the analytical form of the received power from moving target has been obtained. Using the simulated forward scattering radar cross section, the received power of theoretical calculation is near to that of measured data. In addition, the simulated signal model of ground moving target is perfectly matched with the experimented data. All these results show the correctness of analytical calculation completely.

Novel targeting approaches and signaling pathways of colorectal cancer: An insight

Colorectal cancer(CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog(SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a stepwise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virusdirected enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.

Fibroblast growth factor receptor signaling as therapeutic targets in gastric cancer

Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survival of several types of tumor cells. FGFR-induced alterations, including gene amplification, chromosomal translocation, and mutations, have been shown to be associated with the tumor initiation and progression of gastric cancer, especially in diffuse-type cancers. Therefore, the FGFR signaling pathway might be one of the therapeutic targets in gastric cancer. This review aims to provide an overview of the role of FGFR signaling in tumorigenesis, tumor progression, proliferation, and chemoresistance. We also discuss the accumulating evidence that demonstrates the effectiveness of using clinical therapeutic agents to inhibit FGFR signaling for the treatment of gastric cancer.

Mitochondrial targeting sequence of magnetoreceptor MagR:More than just targeting

Iron-sulfur clusters(ISC)are essential cofactors for proteins involved in various biological processes,such as electron transport,biosynthetic reactions,DNA repair,and gene expression regulation.ISC assembly protein IscA1(or MagR)is found within the mitochondria of most eukaryotes.Magnetoreceptor(MagR)is a highly conserved A-type iron and iron-sulfur cluster-binding protein,characterized by two distinct types of iron-sulfur clusters,[2Fe-2S]and[3Fe-4S],each conferring unique magnetic properties.MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome(Cry)and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation.Although the N-terminal sequences of MagR vary among species,their specific function remains unknown.In the present study,we found that the N-terminal sequences of pigeon MagR,previously thought to serve as a mitochondrial targeting signal(MTS),were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound.Moreover,the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex.Thus,the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting.These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.

New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.

Effects of Dietary Soy Protein Concentrate on Growth, Digestive Enzymes Activities and Target of Rapamycin Signaling Pathway Regulation in Juvenile Soft-Shelled Turtle, <i>Pelodiscus sinensis</i>

Soft-shelled turtle, Pelodiscus sinensis is important aquatic species in China, and searching for alternatives protein resources to fish meal (FM)-based feeds in feed has become urgent and important for its sustainability development. The present study was conducted to assess the effects of dietary soy protein concentrate (SPC) on growth, digestive enzymes and target of rapamycin (TOR) signaling pathway of juvenile P. sinensis (4.56 ± 0.09 g). SPC was applied to replace FM protein at 0%, 15%, 30% and 60% (designated as T0, T15, T30 and T60, respectively), and each diet was fed to triplicate groups. The results showed that there was no significant difference in growth performance and feed utilization except of the turtles fed with T60 diet, of which showed poorer daily weight gain and feed conversion rate. The pepsin/trypsin and Na+-K+ ATP-ase activities decreased dramatically when SPC level increased, and lipase activities in liver and intestinal tract also showed decline tendency. However, amylase activities were unaffected. No significant differences were observed in TOR, S6K1 and 4E-BP1 genes mRNA expression level of TOR signaling pathway among the treatments. However, the relative phosphorylated level of these proteins decreased significantly when SPC level increased. The present study indicated that high SPC substitution level would suppress digestive enzymes and TOR signaling pathway proteins phosphorylated level and eventually result in growth reduction of P. sinensis.

Osteopontin promotes gastric cancer progression via phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors.Osteopontin(OPN)is thought to be closely related to the occurrence,metastasis and prognosis of many types of tumors.AIM To investigate the effects of OPN on the proliferation,invasion and migration of GC cells and its possible mechanism.METHODS The mRNA and protein expression of OPN in the GC cells were analyzed by realtime quantitative-reverse transcription polymerase chain reaction and western blotting,and observe the effect of varying degree expression OPN on the proliferation and other behaviors of GC.Next,the effects of OPN knockdown on GC cells migration and invasion were examined.The short hairpin RNA(shRNA)and negative control shRNA targeting OPN-shRNA were transfected into the cells according to the manufacturer’s instructions.Non transfected cells were classified as control in the identical transfecting process.24 h after RNA transfection cell proliferation activity was detected by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide assay,and cell invasiveness and migration were detected by Trans well assay.Meanwhile,the expression of protein kinase B(AKT),matrix metalloproteinase 2(MMP-2)and vascular endothelial growth factor(VEGF)in the human GC cell lines was detected by reverse transcription polymerase chain reaction and western blotting.RESULTS The results of this study revealed that OPN mRNA and protein expression levels were highly expressed in SGC-7901 cells.OPN knockdown by specific shRNA noticeably reduced the capabilities of proliferation,invasion and migration of SGC-7901 cells.Moreover,in the experiments of investigating the underlying mechanism,results showed that OPN knockdown could down-regulated the expression of MMP-2 and VEGF,it also decreased the phosphorylation of AKT.Meanwhile,the protein expression levels of MMP-2,VEGF and phosphorylated AKT was noticeable lower than that in control group in the GC cells after they were added to phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002).CONCLUSION These results suggested that OPN though PI3K/AKT/mammalian target of rapamycin signal pathway to upregulate MMP-2 and VEGF expression,which contribute SGC-7901 cells to proliferation,invasion and migration.Thus,our results demonstrate that OPN may serve as a novel prognostic biomarkers as well as a potential therapeutic targets for GC.

Regenerative potential of targeting glycogen synthase kinase-3 signaling in neural tissues

Multiple roles of glycogen synthase kinase-3（GSK-3）in neural tissues：GSK-3 is a serine/threonine kinase that has two isoforms encoded by two different genes,GSK-3αand GSK-3β,in mammals.GSK-3 has several sites of serine and tyrosine phosphorylation.

Bone morphogenetic protein signaling：a promising target for white matter protection in perinatal brain injury

Prematurely born newborns,as well as those born at term,may suffer from several types of brain injury including hypoxic-ischemic injury,intracranial hemorrhage,both intraventricular and parenchymal,and injury that is the consequence of intrauterine growth restriction（IUGR）.Injury of all types can impact the motor and cognitive abilities of survivors.The mechanisms leading to disability are not completely understood.

Radar-Based Multi-Target Localization and Vital Sign Monitoring

The frequency-modulated continuous wave (FMCW) radar, known for its high range resolution, has garnered significant attention in the field of non-contact vital sign monitoring. However, accurately locating multiple targets and separating their vital sign signals remains a challenging research topic. This paper proposes a scene-differentiated method for multi-target localization and vital sign monitoring. The approach identifies the relative positions of multiple targets using Range FFT and determines the directions of targets via the multiple signal classification (MUSIC) algorithm. Phase signals within the range bins corresponding to the targets are separated using bandpass filtering. If multiple targets reside in the same range bin, the variational mode decomposition (VMD) algorithm is employed to decompose their breathing or heartbeat signals. Experimental results demonstrate that the proposed method accurately localizes targets. When multiple targets occupy the same range bin, the mean absolute error (MAE) for respiratory signals is 3 bpm, and the MAE for heartbeat signals is 5 bpm.

椎间盘退变中的力学信号转导蛋白

背景:近年来的研究表明椎间盘退变与异常压力负荷密切相关,而力学信号转导蛋白在其中发挥了关键作用。目的:探讨力学信号转导蛋白在异常机械力刺激诱导椎间盘退变的力化学信号换能过程中发挥的作用及机制,总结目前靶向力学信号延缓椎间盘退变的治疗策略。方法:以“椎间盘,髓核,纤维环,软骨终板,细胞,力,信号转导,蛋白,生物力学”为中文检索词,以“intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics”为英文检索词,检索PubMed、CNKI数据库中的相关文献,最终纳入88篇文献进行综述。结果与结论:椎间盘细胞能通过多种力学信号转导蛋白感知外界机械刺激并将其转化为细胞内生物学反应,这些转导蛋白主要包括细胞外基质中的胶原蛋白、细胞膜表面受体(如整合素及离子通道)、细胞骨架结构蛋白等。力学信号转导蛋白调控力化学信号换能的过程主要包括多个通路的激活,如PI3K/AKT信号通路、核因子κB信号通路、Ca^(2+)/Calpain2/Caspase3通路等。力学信号转导蛋白在椎间盘细胞机械信号换能中发挥了关键作用,这些蛋白表达异常或由此导致的细胞外基质环境改变会破坏椎间盘细胞的力学平衡,引发椎间盘退变。深入研究椎间盘细胞力学信号转导蛋白的表达及调控机制,寻找关键的病理环节和治疗靶点,对开发椎间盘退变治疗策略具有重要意义,目前靶向力学信号延缓椎间盘退变的策略主要包括对转导蛋白的调控、对细胞外基质的改良等,然而这方面研究还处于初级阶段,随着研究的不断深入,力学信号转导蛋白调控椎间盘退变有望实现新的突破。

A Method to Obtain the Moving Speed of Uncooperative Target Based on Only Two Measurements

The existing research results show that a fixed single station must conduct three consecutive frequency shift measurements and obtain the target’s moving speed by constructing two frequency difference equations. This article proposes a new method that requires only two consecutive measurements. While using the azimuth measurement to obtain the angular difference between two radial distances, it also conducts two consecutive Doppler frequency shift measurements at the same target azimuth. On the basis of this measurement, a frequency difference equation is first constructed and solved jointly with the Doppler frequency shift equation. By eliminating the velocity variable and using the measured angular difference to obtain the target’s lead angle, the target’s velocity can be solved by using the Doppler frequency shift equation again. The new method avoids the condition that the target must move equidistantly, which not only provides an achievable method for engineering applications but also lays a good foundation for further exploring the use of steady-state signals to achieve passive positioning.

小分子药物治疗骨关节炎的热点问题及应用前景

背景:骨关节炎的病理生理过程中存在多种蛋白、信号通路及炎症递质等的参与,开发针对这些蛋白、信号通路及炎症递质等的小分子药物,可有效延缓骨关节炎的进展并改善其临床表现。目的:基于骨关节炎的发病机制,对小分子药物治疗骨关节炎的研究进展作一综述。方法:检索PubMed、中国知网和万方数据库,英文检索词为“osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents”,中文检索词为“骨关节炎,小分子药物,小分子抑制剂”,按纳入和排除标准共纳入68篇文献进行总结。结果与结论:①目前对于骨关节炎发病机制的研究尚不明确,骨关节炎的发生发展与蛋白质、细胞因子及信号转导通路的关系较为密切,因此其治疗机制较为复杂,当前通过小分子药物靶向骨关节炎相关的蛋白质、细胞因子及信号转导通路成为一大研究热点。②小分子药物通常具有明确的细胞内或细胞外靶点和疗效,包括增强软骨修复、抑制关节退化、减轻炎症和缓解疼痛,另外一些抗骨关节炎的小分子药物在促进干细胞软骨分化和软骨基质重建方面显示出前景。③目前对于小分子药物靶向骨关节炎的病理生理过程从而延缓骨关节炎的进展,还处于实验性阶段,但这些小分子药物在实验过程中大部分都表现出预期的结果,目前并无相关研究说明小分子药物治疗骨关节炎的疗效。④小分子药物治疗骨关节炎在基础实验阶段已经达到了预期的实验结果,大量研究表明,小分子药物可以靶向抑制引起骨关节炎的特定蛋白质、细胞因子及信号转导通路,从而治疗骨关节炎,但其安全性和有效性等问题还需要进一步的基础和临床研究进行验证,这一过程需要更多的学者进行探索和研究。⑤目前国内外有许多学者针对骨关节炎的治疗做出了贡献,比起传统治疗方式而言,小分子药物在基础实验阶段表现出更好的疗效和安全性,有望成为未来骨关节炎治疗的新兴方法,为骨关节炎患者摆脱痛苦。

Molecular regulation of vasculogenic mimicry in tumors and potential tumor-target therapy

"Vasculogenic mimicry(VM)",is a term that describes the unique ability of highly aggressive tumor cells to express a multipotent,stem cell-like phenotype,and form a pattern of vasculogenic-like networks in threedimensional culture.As an angiogenesis-independent pathway,VM and/or periodic acid-schiff-positive patterns are associated with poor prognosis in tumor patients.Moreover,VM is resistant to angiogenesis inhibitors.Here,we will review the advances in research on biochemical and molecular signaling pathways of VM in tumors and on potential anti-VM therapy strategy.

New method of time-frequency representation for ISAR imaging of ship targets

Inverse synthetic aperture radar （ISAR） imaging of ship targets is very important in the national defense. For the high maneuverability of ship targets, the Doppler frequency shift of the received signal is time-varying, which will degrade the ISAR image quality for the traditional range-Doppler （RD） algorithm. In this paper, the received signal in a range bin is characterized as the multi-component polynomial phase signal （PPS） after the motion compensation, and a new approach of time-frequency represen- tation, generalized polynomial Wigner-Ville distribution （GPWVD）, is proposed for the azimuth focusing. The GPWVD is based on the exponential matched-phase （EMP） principle. Compared with the conventional polynomial Wigner-Ville distribution （PWVD）, the EMP principle transfers the non-integer lag coefficients of the PWVD to the position of the exponential of the signal, and the interpolation can be avoided completely. For the GPWVD, the cross-terms between multi-component signals can be reduced by decomposing the GPWVD into the convolution of Wigner-Ville distribution （WVD） and the spectrum of phase adjust functions. The GPWVD is used in the ISAR imaging of ship targets, and the high quality instantaneous ISAR images can be obtained. Simulation results and measurement data demonstrate the effectiveness of the proposed new method.

Changing strategies for target therapy in gastric cancer

In spite of a worldwide decrease in the incidence of gastric cancer, this malignancy still remains one of the leading causes of cancer mortality. Great efforts have been made to improve treatment outcomes in patients with metastatic gastric cancer, and the introduction of trastuzumab has greatly improved the overall survival. The trastuzumab treatment took its first step in opening the era of molecular targeted therapy, however several issues still need to be resolved to increase the efficacy of targeted therapy. Firstly, many patients with metastatic gastric cancer who receive trastuzumab in combination with chemotherapeutic agents develop resistance to the targeted therapy. Secondly, many clinical trials testing novel molecular targeted agents with demonstrated efficacy in other malignancies have failed to show benefit in patients with metastatic gastric cancer, suggesting the importance of the selection of appropriate indications according to molecular characteristics in application of targeted agents. Herein, we review the molecular targeted agents currently approved and in use, and clinical trials in patients with metastatic gastric cancer, and demonstrate the limitations and future direction in treatment of advanced gastric cancer.

Hedgehog signaling pathway and ovarian cancer

Epithelial ovarian carcinoma （EOC） is the most common form of ovarian malignancies and the most lethal gynecologic malignancy in the United States. To date, in spite of treatment to it with the extensive surgical debulking and chemotherapy, the prognosis of EOC remains dismal. Recently, it has become increasingly clear that in many instances, the signaling and molecular players that control development are the same, and when inappropriately regulated, drive tumorigenesis and cancer development. Here, we discuss the possible involvement of Hedgehog （Hh） pathway in the cellular regulation and development of cancer in the ovaries. Using the in vitro and in vivo assays developed has facilitated the dissection of the mechanisms behind Hh-driven ovarian cancers formation and growth. Based on recent studies, we propose that the inhibition of Hh signaling may interfere with spheroid-like structures in ovarian cancers. The components of the Hh signaling may provide novel drug targets, which could be explored as crucial combinatorial strategies for the treatment of ovarian cancers.

Innate immune targets of hepatitis B virus infection

Approximately 400 million people are chronically infected with hepatitis B virus(HBV) globally despitethe widespread immunization of HBV vaccine and the development of antiviral therapies. The immunopathogenesis of HBV infection is initiated and driven by complexed interactions between the host immune system and the virus. Host immune responses to viral particles and proteins are regarded as the main determinants of viral clearance or persistent infection and hepatocyte injury. Innate immune system is the first defending line of host preventing from virus invasion. It is acknowledged that HBV has developed active tactics to escape innate immune recognition or actively interfere with innate immune signaling pathways and induce immunosuppression, which favor their replication. HBV reduces the expression of pattern-recognition receptors in the innate immune cells in humans. Also, HBV may interrupt different parts of antiviral signaling pathways, leading to the reduced production of antiviral cytokines such as interferons that contribute to HBV immunopathogenesis. A full comprehension of the mechanisms as to how HBV inactivates various elements of the innate immune response to initiate and maintain a persistent infection can be helpful in designing new immunotherapeutic methods for preventing and eradicating the virus. In this review, we aimed to summarize different branches the innate immune targeted by HBV infection. The review paper provides evidence that multiple components of immune responses should be activated in combination with antiviral therapy to disrupt the tolerance to HBV for eliminating HBV infection.

Waveform diversity based sonar system for target localization

A new monostatic array system taking advantage of diverse waveforms to improve the performance of underwater tar- get localization is proposed. Unlike the coherent signals between different elements in common active array, the transmitted signals from different elements here are spatially orthogonal waveforms which allow for array processing in the transit mode and result in an extension of array aperture. The mathematical derivation of Capon estimator for this sonar system is described in detail. And the performance of this orthogonal-waveform based sonar is an- alyzed and compared with that of its phased-array counterpart by water tank experiments. Experimental results show that this sonar system could achieve 12 dB-15 dB additional array gain over its phased-array counterpart, which means a doubling of maximum detection range. Moreover, the angular resolution is significantly improved at lower SNR.