Chemical substances and their activities in sea cucumber Apostichopus japonicus: A review.

Apostichopus japonicus, also known as Stichopus japonicus, with medicinal and food homologous figures, is a globally recognized precious ingredient with extremely high nutritional value. There is no relevant review available through literature search, so this article selects the research articles through the keywords "sea cucumber" and "Apostichopus japonicus (Stichopus japonicus)" in six professional databases, such as Wiley, PubMed, ScienceDirect, ACS, Springer, and Web of Science, from 2000 to the present, summarizing the extraction, isolation, and purification methods for the four major categories (polysaccharides, proteins and peptides, saponins, and other components) of the A. japonicus chemical substances and 10 effective biological activities of A. japonicus. Included are anticoagulation, anticancer/antitumor activities, hematopoiesis, regulation of gut microbiota, and immune regulatory activities that correspond to traditional efficacy. Literature support is provided for the development of medicines and functional foods and related aspects that play a leading role in future directions.

Kalopanax septemlobus: its phytochemistry, pharmacology and toxicity (1966-2022).

Kalopanax septemlobus is a traditional herbal medicine for multiple medicinal sites (root, stem bark, bark, leaves) in East Asia, and its bark has a significant curative effect on rheumatoid arthritis. In the past 13 years (2009-2022), the research literature accounted for 50% of the total, and it is becoming a research highlight of the relevant international scholars (ACS, ScienceDirect, PubMed, Springer, and Web of Science). This paper is the first comprehensive review of its chemistry, pharmacology, and toxicity for more than half a century (1966-2022), in which the chemical studies include triterpenoids & saponins (86 compounds), and phenylpropanoids (26 compounds), involving 46 new structures and one biomarker-triterpenoid saponin (Kalopanaxsaponin A); According to the number of literature, the pharmacological effects and mechanisms are systematically divided into five aspects, such as: anti-inflammatory, anti-tumor, antioxidant, antifungal and anti-diabetic, etc., covering its toxicological progress. To provide literature support for the exploration of new drugs against related diseases, such as rheumatoid arthritis, which are becoming younger nowadays.

Targeted delivery of nuclear targeting probe for bladder cancer using cyclic pentapeptide c(RGDfK) and acridine orange

Purpose Both cyclic pentapeptide c(RGDfK) and acridine orange (AO) exhibit antitumor effects and cell permeability. This study aimed to evaluate the nuclear targeting efficiency and safety of the nuclear targeting probe for bladder cancer (BCa) synthesized by c(RGDfK) and AO. Tethods The nuclear targeting probe AO-(cRGDfK)2 was synthesized from AO hydrochloride, azided c(RGDfK), and a near-infrared skeleton synthesized via click chemistry reactions. The effect of the AO-(cRGDfK)2 probe on cell viability was assessed in BCa 5637 cells. The tumor cell targeting efficacy of the AO-(cRGDfK)2 probe was evaluated in BCa cells in vitro and in tumor-bearing mice in vivo. Nuclear-specific accumulation of fluorescence probe in BCa tumor cells was evaluated using laser scanning confocal microscopy (LSCM). Hematoxylin and eosin staining was performed to detect histopathological changes in the spleen, heart, liver, and kidney. Results The AO-(cRGDfK)2 probe did not cause a significant reduction in cell viability. LSCM analysis showed that AO-(cRGDfK)2 exhibited nuclear-specific ambulation in BCa cells and was not accumulated in 293T cells. Also, this probe efficiently targeted tumor cells in the serum and urine samples. In vivo imaging system of tumor-bearing mice showed that ~ 80% percent of fluorescence signal was accumulated in the tumor sites. The probe did not change histopathology in the heart, liver, spleen, and kidney in tumor-bearing mice after the 21-day treatment. Conclusions The AO-(cRGDfK)2 probe exhibited nuclear-specific accumulation in BCa cells without cytotoxicity, which provides an innovative alternative to improve anticancer therapy for BCa (AU)

Targeted delivery of nuclear targeting probe for bladder cancer using cyclic pentapeptide c(RGDfK) and acridine orange.

PURPOSE: Both cyclic pentapeptide c(RGDfK) and acridine orange (AO) exhibit antitumor effects and cell permeability. This study aimed to evaluate the nuclear targeting efficiency and safety of the nuclear targeting probe for bladder cancer (BCa) synthesized by c(RGDfK) and AO. METHODS: The nuclear targeting probe AO-(cRGDfK)2 was synthesized from AO hydrochloride, azided c(RGDfK), and a near-infrared skeleton synthesized via click chemistry reactions. The effect of the AO-(cRGDfK)2 probe on cell viability was assessed in BCa 5637 cells. The tumor cell targeting efficacy of the AO-(cRGDfK)2 probe was evaluated in BCa cells in vitro and in tumor-bearing mice in vivo. Nuclear-specific accumulation of fluorescence probe in BCa tumor cells was evaluated using laser scanning confocal microscopy (LSCM). Hematoxylin and eosin staining was performed to detect histopathological changes in the spleen, heart, liver, and kidney. RESULTS: The AO-(cRGDfK)2 probe did not cause a significant reduction in cell viability. LSCM analysis showed that AO-(cRGDfK)2 exhibited nuclear-specific ambulation in BCa cells and was not accumulated in 293T cells. Also, this probe efficiently targeted tumor cells in the serum and urine samples. In vivo imaging system of tumor-bearing mice showed that ~ 80% percent of fluorescence signal was accumulated in the tumor sites. The probe did not change histopathology in the heart, liver, spleen, and kidney in tumor-bearing mice after the 21-day treatment. CONCLUSIONS: The AO-(cRGDfK)2 probe exhibited nuclear-specific accumulation in BCa cells without cytotoxicity, which provides an innovative alternative to improve anticancer therapy for BCa.

Research progress of therapeutic effects and drug resistance of immunotherapy based on PD-1/PD-L1 blockade.

The binding of programmed death-1 (PD-1) on the surface of T cells and PD-1 ligand 1 (PD-L1) on tumor cells can prevent the immune-killing effect of T cells on tumor cells and promote the immune escape of tumor cells. Therefore, immune checkpoint blockade targeting PD-1/PD-L1 is a reliable tumor therapy with remarkable efficacy. However, the main challenges of this therapy are low response rate and acquired resistance, so that the outcomes of this therapy are usually unsatisfactory. This review begins with the description of biological structure of the PD-1/PD-L1 immune checkpoint and its role in a variety of cells. Subsequently, the therapeutic effects of immune checkpoint blockers (PD-1 / PD-L1 inhibitors) in various tumors were introduced and analyzed, and the reasons affecting the function of PD-1/PD-L1 were systematically analyzed. Then, we focused on analyzing, sorting out and introducing the possible underlying mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade including abnormal expression of PD-1/PD-L1 and some factors, immune-related pathways, tumor immune microenvironment, and T cell dysfunction and others. Finally, promising therapeutic strategies to sensitize the resistant patients with PD-1/PD-L1 blockade treatment were described. This review is aimed at providing guidance for the treatment of various tumors, and highlighting the drug resistance mechanisms to offer directions for future tumor treatment and improvement of patient prognosis.

Identification and analysis of microRNA editing events in recurrent bladder cancer based on RNA sequencing: MicroRNA editing level is a potential novel biomarker.

Background: With the continued advancement of RNA-seq (RNA-sequencing), microRNA (miRNA) editing events have been demonstrated to play an important role in different malignancies. However, there is yet no description of the miRNA editing events in recurrent bladder cancer. Objective: To identify and compare miRNA editing events in primary and recurrent bladder cancer, as well as to investigate the potential molecular mechanism and its impact on patient prognosis. Methods: We examined the mRNA and miRNA transcriptomes of 12 recurrent bladder cancer cases and 13 primary bladder cancer cases. The differentially expressed mRNA sequences were analyzed. Furthermore, we identified the differentially expressed genes (DEGs) in recurrent bladder cancer. The Gene Ontology (GO) functional enrichment analyses on DEGs and gene set enrichment analysis were performed. The consensus molecular subtype (CMS) classification of bladder cancer was identified using the Consensus MIBC package in R (4.1.0); miRNA sequences were then further subjected to differentially expressed analysis and pathway enrichment analysis. MiRNA editing events were identified using miRge3.0. miRDB and TargetScanHuman were used to predict the downstream targets of specific differentially edited or expressed miRNAs. The expression levels of miR-154-5p and ADAR were validated by RT-qPCR. Finally, survival and co-expression studies were performed on the TCGA-BLCA cohort. Results: First, the mRNA expression levels in recurrent bladder cancer changed significantly, supporting progression via related molecular signal pathways. Second, significantly altered miRNAs in recurrent bladder cancer were identified, with miR-154-5p showing the highest level of editing in recurrent bladder cancer and may up-regulate the expression levels of downstream targets HS3ST3A1, AQP9, MYLK, and RAB23. The survival analysis results of TCGA data revealed that highly expressed HS3ST3A1 and RAB23 exhibited poor prognosis. In addition, miR-154 editing events were found to be significant to CMS classification. Conclusion: MiRNA editing in recurrent bladder cancer was detected and linked with poor patient prognosis, providing a reference for further uncovering the intricate molecular mechanism in recurrent bladder cancer. Therefore, inhibiting A-to-I editing of miRNA may be a viable target for bladder cancer treatment, allowing current treatment choices to be expanded and individualized.

Targeting HNRNPU to overcome cisplatin resistance in bladder cancer.

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.

Simulation and Experimental Study on Reverse Helical Milling with the Gradual-Removal Reverse Edge Milling Cutter under Ultrasonic-Assisted Condition.

As a new machining method, ultrasonic-assisted bi-direction helical milling has obvious advantages in making holes on carbon fiber-reinforced plastics (CFRP). However, cutting edges of the flat-bottomed milling cutter are easy to wear, which may cause severe defects such as burrs and tears in the outlet of the hole. In order to improve the hole-making quality of CFRP, the gradual-removal reverse edge milling cutter was proposed and designed. The finite method models of reverse helical milling CFRP with the flat-bottomed reverse edge milling cutter and the gradual-removal reverse edge milling cutter under an ultrasonic vibration were established, and the comparative cutting experiments of the two cutters were carried out. By comparing the cutting performance of the two milling cutters under the condition of ultrasonic vibration assistance, the cutting mechanism of improving the hole wall quality by the gradual-removal reverse edge milling cutter was studied. The results showed that when the reverse cumulative cutting depth reached about 60 mm, compared with the flat-bottomed reverse edge milling cutter, the gradual-removal reverse edge milling cutter transferred part of the cutting task of the peripheral edge to the end edge, and the wear of the reverse peripheral edges which directly affects the hole quality was effectively alleviated. This mechanism made the cutting state of the peripheral edge dominated by shear failure, which led to the significant improvement of the quality at the outlet of the hole.

Quercus salicina Blume: Research Progress in Chemistry and Pharmacodynamics (1959-2021).

The crude extracts of different parts (leaves and shoots) of Quercus salicina Blume (QS) have shown considerable effect in urolithiasis. QS has been widely used in clinical practice and has attracted great research interest The relevant published literature, however, reveals only partial education of its chemical components and bio-active mechanisms, and only two review articles have summarized the QS research progress. In this review, a comprehensive and systematic review of chemistry and pharmacodynamics of QS was carried out using the international authoritative databases (1959-2021), focusing on phenols and flavonoids, and their effect such as urinary stone dissolution, anti-inflammatory, anti-diabetes, anti-bacterial, antioxidant, and anti-allergy activities as well as toxic effects. The aim of review is to provide the most recent and effective literature support for further basic research and application development.

Photon-Gated Spin Transistor.

A new type of spin transistor with an optical gate is proposed with partial exposure of the device, where spin scattering is enhanced under light illumination due to the photon-induced minor spins. Consequently a reproducible transient gate operation of reisitance via optical methods is observed, as ascribed to the nature of spin excitation.

Implementation of Complete Boolean Logic Functions in Single Complementary Resistive Switch.

The unique complementary switching behaviour of complementary resistive switches (CRSs) makes them very attractive for logic applications. The implementation of complete Boolean logic functions in a single CRS cell is certainly an extremely important step towards the commercialisation of related logic circuits, but it has not been accomplished to date. Here, we report two methods for the implementation of complete Boolean logic functions in a single CRS cell. The first method is based on the intrinsic switchable diode of a peculiar CRS cell that is composed of two anti-serial bipolar resistive switches with a rectifying high resistance state, while the second method is based directly on the complementary switching behaviour itself of any single CRS cell. The feasibilities of both methods have been theoretically predicted and then experimentally demonstrated on the basis of a Ta/Ta2O5/Pt/Ta2O5/Ta CRS cell. Therefore, these two methods-in particular the complementary switching behaviour itself-based method, which has natural immunity to the sneak-path issue of crossbar logic circuits-are believed to be capable of significantly advancing both our understanding and commercialization of related logic circuits. Moreover, peculiar CRS cells have been demonstrated to be feasible for tri-level storage, which can serve as an alternative method of realising ultra-high-density data storage.

Magnetoelectric Coupling Induced by Interfacial Orbital Reconstruction.

Reversible orbital reconstruction driven by ferroelectric polarization modulates the magnetic performance of model ferroelectric/ferromagnetic heterostructures without onerous limitations. Mn-d(x2-y2) orbital occupancy and related interfacial exotic magnetic states are enhanced and weakened by negative and positive electric fields, respectively, filling the missing member-orbital in the mechanism of magnetoelectric coupling and advancing the application of orbitals to microelectronics.

Charge Transfer and Orbital Reconstruction in Strain-Engineered (La,Sr)MnO3/LaNiO3 Heterostructures.

We investigate charge transfer, orbital reconstruction, and the emergence of exchange bias in (La,Sr)MnO3/LaNiO3 heterostructures. We demonstrate that charge transfer from Mn(3+) ions to Ni(3+) ions is accompanied by the formation of hybridized Mn/Ni 3z(2) - r(2) orbits at the interface, instead of strain-stabilized Mn and Ni x(2) - y(2) orbits in the bulk films. In the heterostructures with ultrathin LaNiO3, orbital reconstruction induced by charge transfer results in magnetization frustration of (La,Sr)MnO3 at the interface. But the strain effect exerted by the growth of the LaNiO3 top layer plays a dominant role on orbital reconstruction in the heterostructures with thick LaNiO3, stabilizing 3z(2) - r(2) orbits. In this case, robust spin glass, associated with larger magnetization frustration, accounts for the exchange bias effect. Our work builds a bridge between the microscopic electronic structure and the macroscopic magnetic property, providing the possibility of manipulating the exotic states with the aid of strain engineering in oxide-based electronics.

Electrical control of the exchange spring in antiferromagnetic metals.

Electrical control of the exchange spring in antiferromagnetic metals is obtained in [Co/Pt]/IrMn Hall devices by using an ionic liquid, where the exchange spring could transfer the "force" and enable a deeper modulation depth in the IrMn. This work provides a new approach toward electrical modulation of the spin structures in metallic antiferromagnets, which should be significant in advancing the development of low-power-consumption antiferromagnet (AFM) spintronics.

Tuning the switching behavior of binary oxide-based resistive memory devices by inserting an ultra-thin chemically active metal nanolayer: a case study on the Ta2O5-Ta system.

The common nonpolar switching behavior of binary oxide-based resistive random access memory devices (RRAMs) has several drawbacks in future application, such as the requirements for a high forming voltage, a large reset current, and an additional access device to settle the sneak-path issue. Herein, we propose the tuning of the switching behavior of binary oxide-based RRAMs by inserting an ultra-thin chemically active metal nanolayer, and a case study on Ta2O5-Ta systems is provided. The devices are designed to be Pt/Ta2O5(5 - x/2)/Ta(x)/Ta2O5(5 - x/2)/Pt with x = 0, 2, or 4 nm. The reference devices without the Ta nanolayer exhibit an expected nonpolar switching behavior with a high forming voltage of ∼-4.5 V and a large reset current of >10 mA. In contrast, a self-compliance bipolar switching behavior with a low forming voltage of ∼-2 V and a small reset current of <1 mA is observed after inserting a 2 nm Ta nanolayer. When the Ta nanolayer is increased to 4 nm, a complementary resistive switching (CRS) behavior is found, which can effectively settle the sneak-path issue. The appearance of CRS behavior suggests that a thin Ta nanolayer of 4 nm is robust enough to act as an inner electrode. Besides, the behind switching mechanisms are thoroughly discussed with the help of a transmission electron microscope and temperature-dependent electrical measurements. All these results demonstrate the feasibility of tuning switching behavior of binary oxide-based RRAMs by inserting an ultra-thin chemically active metal nanolayer and might help to advance the commercialization of binary oxide-based RRAMs.

Forming-free and self-rectifying resistive switching of the simple Pt/TaOx/n-Si structure for access device-free high-density memory application.

The search for self-rectifying resistive memories has aroused great attention due to their potential in high-density memory applications without additional access devices. Here we report the forming-free and self-rectifying bipolar resistive switching behavior of a simple Pt/TaOx/n-Si tri-layer structure. The forming-free phenomenon is attributed to the generation of a large amount of oxygen vacancies, in a TaOx region that is in close proximity to the TaOx/n-Si interface, via out-diffusion of oxygen ions from TaOx to n-Si. A maximum rectification ratio of ∼6 × 10(2) is obtained when the Pt/TaOx/n-Si devices stay in a low resistance state, which originates from the existence of a Schottky barrier between the formed oxygen vacancy filament and the n-Si electrode. More importantly, numerical simulation reveals that the self-rectifying behavior itself can guarantee a maximum crossbar size of 212 × 212 (∼44 kbit) on the premise of 10% read margin. Moreover, satisfactory switching uniformity and retention performance are observed based on this simple tri-layer structure. All of these results demonstrate the great potential of this simple Pt/TaOx/n-Si tri-layer structure for access device-free high-density memory applications.

Contributions of magnetic properties in epitaxial copper-doped ZnO.

Diluted magnetic semiconductors have great potential in applications for biological detection and spintronics. However, the origin of magnetism is complex and it is of significant importance to clarify the contributions from various origins. We prepared epitaxial copper-doped ZnO films and investigated the origin of ferromagnetism by combining various characterization methods. The results show that, with nominal Cu concentrations of up to 7.3 at.%, the Cu atoms substitute for the Zn atoms and form strong covalence bonds (Cu(Zn)-O), which show a property commensurate with that of the Zn-O bonds in the ZnO host. With further increases in Cu concentrations, the substitutional Cu(Zn) effect is obscured, and the [Cu(Zn)O4] clusters, regulated by the wurtzite ZnO host, segregate into CuO phase after annealing in air. Magnetization in volume increases with increasing Cu content up to about 7.3 at.% and then decreases with further increase, while the magnetic moment per Cu atom decreases monotonically with the increase in Cu content. We have demonstrated that the substitution of Cu for Zn and the presence of strong Cu(Zn)-O bonds are necessary for ferromagnetism while the [Cu(Zn)O4] clusters are detrimental to the ferromagnetism. The enhancement of ferromagnetism in volume is strongly correlated with the moderate oxygen vacancy mediated Cu ions.

Effect of electrode materials on AlN-based bipolar and complementary resistive switching.

We report the complementary resistive switching (CRS) behaviors in aluminum nitride (AlN)-based memory devices as the promising new material system for large-scale integration of passive crossbar arrays. By utilizing different electrodes (Cu, Pt, and TiN), CRS characteristics are demonstrated in both TiN/AlN/Cu/AlN/TiN electrochemical metallization cells and Pt/AlN/TiN/AlN/Pt ionic resistive switching systems. The instability of Pt/AlN/Cu/AlN/Pt based CRS is explained by the relatively small reset voltage caused by the thermal effects enhanced reset process in the corresponding bipolar resistive switching element. It is concluded that the prerequisite for reliable and stable CRS is that the reset voltage of the bipolar resistive switching element must be much larger than half of the set voltage.

Structure and variable numbers of tandem repeats (VNTRs) of the mitochondrial control region in mitten crab Eriocheir (Crustacean: Brachyura).

Mitochondrial control region was called "A + T-rich" region in invertebrate. In the study, the general organization of control region in mitten crab was divided into two major domains: high variable segment and conserved segment. Four conserved blocks (CSB1, CSB2, CSB3 and CSB4) and two tandem repeat sequences (RT1 and RT2) were defined in control region. There were 116 polymorphic sites and 84 parsimony information sites in 571 aligned sites of the high variable segment adjacent "tRNA-Gln", in which 58 stable variable sites were defined between E. j. sinensis and E. j. hepuensis. Conserved domain contained more than two similar repeat units, and length polymorphism of control region was due to the number difference between the two repeat units (RT1 and RT2). And length polymorphism was a common phenomenon for tandem repeat in control region in the study. Furthermore, a novel result showed the core nucleotide of RT2 in control region tandem repeat was C in E. j. hepuensis, but G in E. j. sinensis. It might be a rapid and cost-effective measure of seedlings differentiation in aquaculture.

[The role of miR398 in plant stress responses].

MicroRNAs (miRNAs) are a new class of small RNAs, which act as post-transcriptional negative regulators of gene expression. Plant miRNAs are important in the regulation of plant growth, development and in response to various abiotic and biotic stresses. miR398 is the first reported miRNA to be down-regulated by oxidative stresses. miR398 plays an impor-tant role in stresses, such as regulating copper homeostasis, in response to abiotic stresses including heavy metals, sucrose, and ozone and biotic stresses via down-regulating the expression of Cu/Zn-superoxide dismutase (CSD). This review fo-cused on the crucial role of miR398 in regulation of different stresses and the transcriptional regulation of MIR398 gene.