LncRNA AP000842.3 Triggers the Malignant Progression of Prostate Cancer by Regulating Cuproptosis Related Gene NFAT5.

OBJECTIVES: Prostate cancer (PRAD) is a highly malignant disease with poor prognosis, and its development is regulated by a complex network of genes and signaling pathways. LncRNAs and miRNAs have significant regulatory roles in PRAD through the ceRNA network. Cuproptosis is a unique form of programmed cell death that is involved in various signaling pathways and biological processes related to tumor development. Nuclear factor of activated T cells 5 (NFAT5), a transcription factor that activates T cells, has been implicated in cuproptosis. However, the regulatory mechanism by which NFAT5 is involved in the ceRNA network in PRAD remains unclear. METHODS: Through bioinformatics analysis, we found the ceRNA axis that regulates cuproptosis. By performing ROS assay and copper ion concentration assay, we demonstrated that inhibiting NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. By using luciferase assay, we discovered that AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. RESULTS: In this study, we found that lncRNA AP000842.3, as a ceRNA of miR-206, was involved in the regulation of levels of the transcription factor NFAT5 associated with cuproptosis in PRAD. First, knocking down NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. Meanwhile, changes in the expression of AP000842.3 and miR-206 could affect the proliferation of PRAD by regulating NFAT5. Mechanistically, AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. In addition, the effects of lncRNA AP000842.3 on malignant progression of PRAD and NFAT5 were partially dependent on miR-206. CONCLUSION: Taken together, our study reveals a key ceRNA regulatory network in PRAD and can be regarded as a new potential target for PRAD diagnosis and treatment.

Unveiling therapeutic prospects: targeting MDM-2 in non-muscle invasive bladder cancer.

Non-muscle invasive bladder cancer (NMIBC) is considered one of the most costly malignancies, requiring significant surgical and therapeutic measures. However, progression and non-responsiveness to immunotherapy are common outcomes of treatment. In this study, we conducted comparative transcriptomic analysis of non-responders from two distinct populations (Asian and American) and identified six common genes associated with disease prognosis. Among these genes, MDM-2 is a major oncogenic protein linked to seven different types of cancers, as it is involved in the degradation of the tumor suppressor protein p53. To address this, we explored novel therapeutic drugs to block the binding of p53 and MDM-2 using a targeted molecular docking approach. High-throughput screening of 2500 drugs from the FDA-approved drug database led to the identification of three drug compounds: Mol-126, Mol-679, and Mol-768. Subsequently, we evaluated the structural stability and binding of these drugs for the targeted inhibition of the MDM-2 active site (hydrophobic cleft) using molecular dynamics simulations. Analysis of five trajectories, including RMSD, RMSF, hydrogen bond, radius of gyration, coulomb short-range electrostatic spectra, and free binding energy, confirmed that Mol-126 exhibited the highest structural stability compared to the reference drug (Alrizomadlin). Notably, Mol-126 is a derivative of 3-phenoxypropionic acid, which shows promise for the development of alternative therapeutic treatments for non-responsive bladder cancer patients.Communicated by Ramaswamy H. Sarma.

Study of Low-Pressure Cold Spray Additive Manufacturing: Investigation of Kinematic Spray Parameters on Deposition and Properties.

Low-pressure cold spray (LPCS) has broadened the application field of cold spray owing to its portability and low cost. For additive manufacturing (AM) based on LPCS (LPCSAM), it is important to investigate the effects of parameters such as temperature and pressure of the gas, stand-off distance, gun traverse speed, and the number of scanning passes of the gun on the deposition and properties. This study aims to determine the optimal kinematic spray parameters for spraying Cu+Al2O3 powder onto an aluminum substrate through LPCS, so as to prepare for the next AM work. The deposition mass, deposition rate, microhardness, and roughness under different spraying conditions were studied. The best spraying effect, with a high deposition rate and without nozzle clogging, was obtained at a nitrogen pressure of 0.9 MPa and a temperature of 400°C.

Probing the Twist-Controlled Interlayer Coupling in Artificially Stacked Transition Metal Dichalcogenide Bilayers by Second-Harmonic Generation.

Interlayer coupling plays a critical role in the electronic band structures and optoelectronic properties of van der Waals (vdW) materials and heterostructures. Here, we utilize optical second-harmonic generation (SHG) measurements to probe the twist-controlled interlayer coupling in artificially stacked WSe2/WSe2 homobilayers and WSe2/WS2 and WSe2/MoS2 heterobilayers with a postannealing procedure. In the large angle twisted WSe2/WSe2 and WSe2/WS2, the angular dependence of the SHG intensity follows the interference relations up to angles above 10°. For lower angles, the SHG is significantly suppressed. Furthermore, for the twisted WSe2/MoS2 the SHG intensity largely deviates from the coherent superposition model and shows consistent quenching for all the stacking angles. The suppressed SHG in twisted transition metal dichalcogenide (TMDC) bilayers is predominantly attributed to the interlayer coupling between the two adjacent monolayers. The evolution of the interlayer Raman mode in WSe2 demonstrates that the interlayer coupling in the twisted WSe2/WSe2 and WSe2/WS2 is highly angle-dependent. Alternatively, the interlayer coupling generally exists in the twisted WSe2/MoS2, regardless of the different angles. The interlayer coupling is further confirmed by the quenching and red-shift of the photoluminescence of WSe2 in the twisted TMDC bilayers. Combined with density functional theory calculations, we reveal that the stacking-angle-modulated interlayer coupling originates from the variation of the interlayer spacing and the binding energy in the twisted TMDC bilayers.

Evaluation and application of chlorine decay models for humanitarian emergency water supply contexts.

Chlorine is a widely used water disinfectant in humanitarian emergency water supply. However, its effective application can be limited by the uncertainty in initial dose determination. The target free chlorine residual in water should achieve both health objectives and aesthetic considerations, but the varying field conditions and changing source water quality may affect the performance of chlorination strategies. A chlorine dose predictive tool could assist in initial dose determination. To this end, an accurate chlorine decay kinetic model can serve as a strong foundation for developing such a tool. In this study, a literature search identified 7 basic chlorine decay kinetic models that were subsequently tested with 610 different chlorine decay test data (from a semi-systematic literature search and laboratory-generated results). The models were then ranked based on their goodness of fit (R2) and root mean square error. An empirical model, power models and parallel models were found able to fit most decay data with more than half of the regressions resulting in R2 value over 0.97. First order models can achieve R2 value above 0.95 when the data points in the rapid phase are excluded from the model fitting. The power models and parallel models can form a strong basis for developing a chlorine dose predictive tool if the power term and the ratio term (model parameters) can be controlled. An essential next step is to evaluate the relationships between easily obtainable water parameters in the field and the decay term in the models to allow rapid model calibration.

Direct Visualization and Manipulation of Stacking Orders in Few-Layer Graphene by Dynamic Atomic Force Microscopy.

Stacking order plays a central role in governing a wide range of properties in layered two-dimensional materials. In the case of few-layer graphene, there are two common stacking configurations: ABA and ABC stacking, which have been proven to exhibit dramatically different electronic properties. However, the controllable characterization and manipulation between them remain a great challenge. Here, we report that ABA- and ABC-stacked domains can be directly visualized in phase imaging by tapping-mode atomic force microscopy with much higher spatial resolution than conventional optical spectroscopy. The contrasting phase is caused by the different energy dissipation by the tip-sample interaction. We further demonstrate controllable manipulation on the ABA/ABC domain walls by means of propagating stress transverse waves generated by the tapping of tip. Our results offer a reliable strategy for direct imaging and precise control of the atomic structures in few-layer graphene, which can be extended to other two-dimensional materials.

Phase-Changing in Graphite Assisted by Interface Charge Injection.

Among many phase-changing materials, graphite is probably the most studied and interesting: the rhombohedral (3R) and hexagonal (2H) phases exhibit dramatically different electronic properties. However, up to now the only way to promote 3R to 2H phase transition is through exposure to elevated temperatures (above 1000 °C); thus, it is not feasible for modern technology. In this work, we demonstrate that 3R to 2H phase transition can be promoted by changing the charged state of 3D graphite, which promotes the repulsion between the layers and significantly reduces the energy barrier between the 3R and 2H phases. In particular, we show that charge transfer from lithium nitride (α-Li3N) to graphite can lower the transition temperature down to 350 °C. The proposed interlayer slipping model potentially offers the control over topological states at the interfaces between different phases, making this system even more attractive for future electronic applications.

Exploring microRNA target genes and identifying hub genes in bladder cancer based on bioinformatic analysis.

BACKGROUND: Bladder cancer (BC) is the second most frequent malignancy of the urinary system. The aim of this study was to identify key microRNAs (miRNAs) and hub genes associated with BC as well as analyse their targeted relationships. METHODS: According to the microRNA dataset GSE112264 and gene microarray dataset GSE52519, differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using the R limma software package. The FunRich software database was used to predict the miRNA-targeted genes. The overlapping common genes (OCGs) between miRNA-targeted genes and DEGs were screened to construct the PPI network. Then, gene ontology (GO) analysis was performed through the "cluster Profiler" and "org.Hs.eg.db" R packages. The differential expression analysis and hierarchical clustering of these hub genes were analysed through the GEPIA and UCSC Cancer Genomics Browser databases, respectively. KEGG pathway enrichment analyses of hub genes were performed through gene set enrichment analysis (GSEA). RESULTS: A total of 12 DEMs and 10 hub genes were identified. Differential expression analysis of the hub genes using the GEPIA database was consistent with the results for the UCSC Cancer Genomics Browser database. The results indicated that these hub genes were oncogenes, but VCL, TPM2, and TPM1 were tumour suppressor genes. The GSEA also showed that hub genes were most enriched in those pathways that were closely associated with tumour proliferation and apoptosis. CONCLUSIONS: In this study, we built a miRNA-mRNA regulatory targeted network, which explores an understanding of the pathogenesis of cancer development and provides key evidence for novel targeted treatments for BC.

Enhanced Descending Corticomuscular Coupling During Hand Grip With Static Force Compared With Enhancing Force.

The interaction between cortex and muscles under hand motor with different force states has not been quantitatively investigated yet, which to some extent places the optimized movement tasks design for brain-computer interface (BCI) applications in hand motor rehabilitation under uncertainty. Converging evidence has suggested that both the descending corticospinal pathway and ascending sensory feedback pathway are involved in the generation of corticomuscular coupling. The present study aimed to explore the corticomuscular coupling during hand motor task with enhancing force and steady-state force. Twenty healthy subjects performed precision grip with enhancing and static force using the right hand with visual feedback of exerted force. Mutual information and Granger causal connectivity were assessed between electroencephalography (EEG) over primary motor cortex and electromyography (EMG) recordings, and statistically analyzed. The results showed that the mutual information value was significantly larger for static force in the beta and alpha frequency band than enhancing force state. Furthermore, compared with enhancing force, the Granger causal connectivity of descending pathways from cortex to muscle was significantly larger for static force in the beta and high alpha frequency band (10-20 Hz), indicating the connection between the primary motor cortex and muscle was strengthened for static force. In summary, the hand grip with static force resulted in an increasing corticomuscular coupling from EEG over the primary motor cortex to EMG compared with enhancing force, implying more attention was required in the static force state. These results have important implications toward motor rehabilitation therapy design for the recovery of impaired hand motor functions.

Pattern Reorganization of Corticomuscular Connection with the Tactile Stimulation.

Sensitivity to tactile stimuli is an indispensable feedback in human motion control. However, previous studies on tactile stimulation mainly focused on the effects of superficial tactile stimulation on the motor cortex, but the role of deep tactile feedback stimulation in motor tasks is not clear. Corticomuscular coherence (CMC) is an effective method for studying dynamic motion tasks. Recent evidence suggests that CMC is enhanced by tactile stimulation in the beta-band. But, the mechanism of tactile stimulation in dynamic motor tasks is still undetermined. In order to explore the role of tactile stimulation in dynamic motion tasks, we examined the correlation between EEG/EMG in a motor task with tactile stimulus input, including the corticomuscular coherence and the causal connections (convergent cross mapping, CCM). In this study, seventeen subjects were recruited to complete stimuli and non-stimuli motor tasks. After the experiment, the time-frequency analysis of CMC showed that the somatosensory association cortex was clearly involved in the dynamic motor tasks. During the contraction of hand muscles, the activity of CMC was concentrated in gamma band, while in the maintenance process, it was concentrated in beta-band. After eliminating the distractors of attention, we did not find a similar result as previous studies had found-tactile stimuli lead to increased CMC activity in gamma band. On the contrary, CCM causality analysis showed that tactile stimulation could significantly enhance the connection between the cerebral cortex and a muscle. We speculate that tactile stimulation can enhance the corticomuscular causal relationship, and that the effect of tactile stimulation on corticomuscular coherence may have more complex mechanisms. This study provides new insights into neural mechanism of tactile feedback and provides more information about the causality of brain networks in tactile feedback task.

[Review of comprehensive intervention by hand rehabilitation robot after stroke].

Using intelligent rehabilitation robot to intervene hand function after stroke is an important physical treatment. With the development of biomedical engineering and the improvement of clinical demand, the comprehensive intervention of hand-function rehabilitation robot combined with new technologies is gradually emerging. This article summarizes the hand rehabilitation robots based on electromyogram (EMG), the brain-computer interface (BCI) hand rehabilitation robots, the somatosensory hand rehabilitation robots and the hand rehabilitation robots with functional electrostimulation. The advantages and disadvantages of various intervention methods are discussed, and the research trend about comprehensive intervention of hand rehabilitation robot is analyzed.