A novel long non-coding RNA SLNCR1 promotes proliferation, migration, and invasion of melanoma via transcriptionally regulating SOX5.

Steroid receptor RNA activator (SRA)-like non-coding RNA (SLNCR1) has been implicated in various tumorigenic processes, but the precise regulatory role in melanoma progression remains uncertain. We performed a comprehensive analysis to investigate the prognostic value of SLNCR1 expression in patients with melanoma by TCGA database and melanoma tissue samples via the Kaplan-Meier method. Subsequently, we conducted qRT-PCR and Fluorescence in Situ Hybridization (FISH) assays to identify SLNCR1 expression levels and localization in tissues and cells, respectively. Loss-of-function assays utilizing shRNAs vectors were used to investigate the potential impact of SLNCR1. Our data showed that SLNCR1 is significantly up-regulated in human malignant melanoma tissues and cell lines and functions as an oncogene. Silencing of SLNCR1 suppressed melanoma cell proliferation, migration, invasion, and inhibited tumorigenesis in a mouse xenograft model. Additionally, we employed bioinformatic predictive analysis, combined with dual-luciferase reporter analysis and functional rescue assays, to elucidate the mechanistic target of the SLNCR1/SOX5 axis in melanoma. Mechanistically, we discovered that SLNCR1 promotes EMT of human melanoma by targeting SOX5, as downregulation of SLNCR1 expression leads to a decrease in SOX5 protein levels and inhibits melanoma tumorigenesis. Our research offers promising insights for more precise diagnosis and treatment of human melanoma.

Halide Anions Tuning of Lead-Free Perovskite-Type Ferroelectric Semiconductors with Inverse High-Temperature Symmetry Breaking.

There is a noticeable gap in the literature regarding research on halogen-substitution-regulated ferroelectric semiconductors featuring multiple phase transitions. Here, a new category of 1D perovskite ferroelectrics (DFP)2 SbX5 (DFP+ = 3,3-difluoropyrrolidium, X- = I- , Br- , abbreviated as I-1 and Br-2) with twophase transitions (PTs) is reported. The first low-temperature PT is a mmmFmm2 ferroelectric PT, while the high-temperature PT is a counterintuitive inverse temperature symmetry-breaking PT. By the substitution of iodine with bromine, the Curie temperature (Tc) significantly increases from 348 K of I-1 to 374 K of Br-2. Their ferroelectricity and pyroelectricity are improved (Ps value from 1.3 to 4.0 µC cm-2 , pe value from 0.2 to 0.48 µC cm-2  K-1 for I-1 and Br-2), while their optical bandgaps increased from 2.1 to 2.7 eV. A critical slowing down phenomenon is observed in the dielectric measurement of I-1 while Br-2 exhibits the ferroelastic domain. Structural and computational analyses elucidate that the order-disorder movement of cations and the distortion of the chain perovskite [SbX5 ]2- anions skeleton lead to PT. The semiconductor properties are determined by [SbX5 ]2- anions. The findings contribute to the development of ferroelectric semiconductors and materials with multiple PTs and provide materials for potential applications in the optoelectronic field.

OXCT1 functions as a succinyltransferase, contributing to hepatocellular carcinoma via succinylating LACTB.

Metabolic reprogramming is an important feature of cancers that has been closely linked to post-translational protein modification (PTM). Lysine succinylation is a recently identified PTM involved in regulating protein functions, whereas its regulatory mechanism and possible roles in tumor progression remain unclear. Here, we show that OXCT1, an enzyme catalyzing ketone body oxidation, functions as a lysine succinyltransferase to contribute to tumor progression. Mechanistically, we find that OXCT1 functions as a succinyltransferase, with residue G424 essential for this activity. We also identified serine beta-lactamase-like protein (LACTB) as a main target of OXCT1-mediated succinylation. Extensive succinylation of LACTB K284 inhibits its proteolytic activity, resulting in increased mitochondrial membrane potential and respiration, ultimately leading to hepatocellular carcinoma (HCC) progression. In summary, this study establishes lysine succinyltransferase function of OXCT1 and highlights a link between HCC prognosis and LACTB K284 succinylation, suggesting a potentially valuable biomarker and therapeutic target for further development.

An improved Bi-LSTM method based on heterogeneous features fusion and attention mechanism for ECG recognition.

Electrocardiogram (ECG) plays a critical role in early prevention and diagnosis of cardiovascular diseases. However, extracting powerful deep features from ECG signal for recognition is still a challenging problem today due to the variable abnormal rhythms and noise distribution. This work proposes a Bi-LSTM algorithm based on heterogeneous features fusion and attention mechanism (HFFAM + Bi-LSTM). Combining the empirical features and the features learned by the deep learning network, HFFAM + Bi-LSTM can comprehensively extract the temporal frequency information and spatial structure information of the ECG signal. Meanwhile, a novel attention mechanism based on improved DTW (AM-DTW) is designed to analyze and control the fusion process of features. The role of AM-DTW in HFFAM + Bi-LSTM is twofold, one is to measure the feature similarity between ECG signal sets with different labels using the improved DTW, and the other is to distinguish the features into isomorphic and heterogeneous features as well as adaptive weighting of the features. It is worth mentioning that overly similar isomorphic features are filtered out to further optimize the algorithm. Thus, HFFAM + Bi-LSTM has the advantage of strengthening the heterogeneous information in the feature subspace while accounting for the isomorphic features. The accuracy of HFFAM + Bi-LSTM reaches up to 98.1 % and 97.1 % on the simulated and real datasets, respectively. Compared to the all benchmark models, the classification accuracy of HFFAM + Bi-LSTM is 1.3 % higher than the best. The experiments also demonstrate that HFFAM + Bi-LSTM has better performance compared with existing methods, which provides a new scheme for automatic detection of ECG signal.

Charge Characteristics of Dielectric Particle Swarm Involving Comprehensive Electrostatic Information.

The triboelectrification effect caused by dynamic contact between particles is an issue for explosions caused by electrostatic discharging (ESD) in the triboelectric nanogenerators (TENGs) for powering the flexible and wearable sensors. The electrostatic strength of dielectric particles (surface charge density, surface potential, electric field, etc.) is essential to evaluate the level of ESD risk. Those differential electrostatic characteristics concerned with unhomogenized swarmed particles cannot be offered via in-current employed-joint COMSOL 6.1 simulation, in which the discrete charged dielectric particles are mistakenly regarded as continuous ones. In this paper, the hybrid discrete element method (EDEM tool) associated with programming in COMSOL Multiphysics 6.1 with MATLAB R2023a was employed to obtain the electrostatic information of the triboelectric dielectric particle swarm. We revealed that the high-accuracy strengths of electric potential and electric field inside particle warm are crucial to evaluating ESD risk. The calculated electrostatic characteristics differ from the grid method and continuous method in the surface potential and electric field. This EDEM-based simulation method is significant for microcosmic understanding and the assessment of the ESD risk in TENGs.

Toxic effects of sirolimus and everolimus on the development and behavior of zebrafish embryos.

Sirolimus and everolimus have been widely used in children. These mammalian target of rapamycin (mTOR) inhibitors have shown excellent efficacy not only in organ transplant patients as immunosuppressive agents but also in patients with some other diseases. However, whether mTOR inhibitors can affect the growth and development of children is of great concern. In this study, using zebrafish models, we discovered that sirolimus and everolimus could slow the development of zebrafish, affecting indicators such as survival, hatching, deformities, body length, and movement. In addition to these basic indicators, sirolimus and everolimus had certain slowing effects on the growth and development of the nervous system, blood vessels, and the immune system. These effects were dose dependent. When the drug concentration reached or exceeded 0.5 µM, the impacts of sirolimus and everolimus were very significant. More interestingly, the impact was transient. Over time, the various manifestations of experimental embryos gradually approached those of control embryos. We also compared the effects of sirolimus and everolimus on zebrafish, and we revealed that there was no significant difference between these drugs in terms of their effects. In summary, the dose of sirolimus and everolimus in children should be strictly controlled, and the drug concentration should be monitored over time. Otherwise, drug overdosing may have a certain impact on the growth and development of children.

A Comparative and Collaborative Study of the Hydrodynamics of Two Swimming Modes Applicable to Dolphins.

This paper presents a hydrodynamics study that examines the comparison and collaboration of two swimming modes relevant to the universality of dolphins. This study utilizes a three-dimensional virtual swimmer model resembling a dolphin, which comprises a body and/or caudal fin (BCF) module, as well as a medium and/or paired fin (MPF) module, each equipped with predetermined kinematics. The manipulation of the dolphin to simulate various swimming modes is achieved through the application of overlapping grids in conjunction with the parallel hole cutting technique. The findings demonstrate that the swimming velocity and thrust attained through the single BCF mode consistently surpass those achieved through the single MPF mode and collaborative mode. Interestingly, the involvement of the MPF mode does not necessarily contribute to performance enhancement. Nevertheless, it is encouraging to note that adjusting the phase difference between the two modes can partially mitigate the limitations associated with the MPF mode. To further investigate the potential advantages of dual-mode collaboration, we conducted experiments by increasing the MPF frequency while keeping the BCF frequency constant, thus introducing the concept of frequency ratio (ß). In comparison to the single BCF mode, the collaborative mode with a high ß exhibits superior swimming velocity and thrust. Although its efficiency experiences a slight decrease, it tends to stabilize. The corresponding flow structure indirectly verifies the favorable impact of collaboration.

Combined treatment with Sigma1R and A2AR agonists fails to inhibit cocaine self-administration despite causing strong antagonistic accumbal A2AR-D2R complex interactions: the potential role of astrocytes.

Previous studies have indicated that acute treatment with the monoamine stabilizer OSU-6162 (5 mg/kg), which has a high affinity for Sigma1R, significantly increased the density of accumbal shell D2R-Sigma1R and A2AR-D2R heteroreceptor complexes following cocaine self-administration. Ex vivo studies using the A2AR agonist CGS21680 also suggested the existence of enhanced antagonistic accumbal A2AR-D2R allosteric interactions after treatment with OSU-6162 during cocaine self-administration. However, a 3-day treatment with OSU-6162 (5 mg/kg) failed to alter the behavioral effects of cocaine self-administration. To test these results and the relevance of OSU-6162 (2.5 mg/kg) and/or A2AR (0.05 mg/kg) agonist interactions, we administered low doses of receptor agonists during cocaine self-administration and assessed their neurochemical and behavioral effects. No effects were observed on cocaine self-administration; however, marked and highly significant increases using the proximity ligation assay (PLA) were induced by the co-treatment on the density of the A2AR-D2R heterocomplexes in the nucleus accumbens shell. Significant decreases in the affinity of the D2R high- and low-affinity agonist binding sites were also observed. Thus, in low doses, the highly significant neurochemical effects observed upon cotreatment with an A2AR agonist and a Sigma1R ligand on the A2AR-D2R heterocomplexes and their enhancement of allosteric inhibition of D2R high-affinity binding are not linked to the modulation of cocaine self-administration. The explanation may be related to an increased release of ATP and adenosine from astrocytes in the nucleus accumbens shell in cocaine self-administration. This can lead to increased activation of the A1R protomer in a putative A1R-A2AR-D2R complex that modulates glutamate release in the presynaptic glutamate synapse. We hypothesized that the integration of changes in presynaptic glutamate release and postjunctional heteroreceptor complex signaling, where D2R plays a key role, result in no changes in the firing of the GABA anti-reward neurons, resulting in no reduction in cocaine self-administration in the present experiments.

Fatigue Behavior of Sandstone Exposed to Cyclic Point-Loading: Implications for Improving Mechanized Rock Breakage Efficiency.

During the process of mechanized excavation, rock is essentially subjected to cyclic point loading (CPL). To understand the CPL fatigue behavior of rock materials, a series of CPL tests are conducted on sandstone samples by using a self-developed vibration point-load apparatus. The effects of loading frequency and waveform on rock fatigue properties under CPL conditions are specifically investigated. The load and indentation depth histories of sandstone samples during testing are monitored and logged. The variation trends of fatigue life (failure time) under different loading conditions are obtained. Test results indicate that the fatigue life of the sandstone sample exposed to CPL is dependent on both loading frequency and waveform. As the loading frequency rises, the fatigue life of the sandstone first declines and then increases, and it becomes the lowest at 0.5 Hz. In terms of waveform, the fatigue life of the sandstone is largest under the trigonal wave and is least under the rectangular wave. These findings can provide valuable theoretical support for optimizing the rock cutting parameters to enhance the efficiency of mechanized excavation.

Non-Hermitian Topolectrical Circuit Sensor with High Sensitivity.

Electronic sensors play important roles in various applications, such as industry and environmental monitoring, biomedical sample ingredient analysis, wireless networks and so on. However, the sensitivity and robustness of current schemes are often limited by the low quality-factors of resonators and fabrication disorders. Hence, exploring new mechanisms of the electronic sensor with a high-level sensitivity and a strong robustness is of great significance. Here, a new way to design electronic sensors with superior performances based on exotic properties of non-Hermitian topological physics is proposed. Owing to the extreme boundary-sensitivity of non-Hermitian topological zero modes, the frequency shift induced by boundary perturbations can show an exponential growth trend with respect to the size of non-Hermitian topolectrical circuit sensors. Moreover, such an exponential growth sensitivity is also robust against disorders of circuit elements. Using designed non-Hermitian topolectrical circuit sensors, the ultrasensitive identification of the distance, rotation angle, and liquid level is further experimentally verified with the designed capacitive devices. The proposed non-Hermitian topolectrical circuit sensors can possess a wide range of applications in ultrasensitive environmental monitoring and show an exciting prospect for next-generation sensing technologies.

Secreted protease PRSS35 suppresses hepatocellular carcinoma by disabling CXCL2-mediated neutrophil extracellular traps.

Hepatocytes function largely through the secretion of proteins that regulate cell proliferation, metabolism, and intercellular communications. During the progression of hepatocellular carcinoma (HCC), the hepatocyte secretome changes dynamically as both a consequence and a causative factor in tumorigenesis, although the full scope of secreted protein function in this process remains unclear. Here, we show that the secreted pseudo serine protease PRSS35 functions as a tumor suppressor in HCC. Mechanistically, we demonstrate that active PRSS35 is processed via cleavage by proprotein convertases. Active PRSS35 then suppresses protein levels of CXCL2 through targeted cleavage of tandem lysine (KK) recognition motif. Consequently, CXCL2 degradation attenuates neutrophil recruitment to tumors and formation of neutrophil extracellular traps, ultimately suppressing HCC progression. These findings expand our understanding of the hepatocyte secretome's role in cancer development while providing a basis for the clinical translation of PRRS35 as a therapeutic target or diagnostic biomarker.

Understanding the Role of Soft X-ray in Charging Solid-Film and Cellular Electrets.

Solid-film electrets and cellular electrets are defined as promising insulating dielectric materials containing permanent electrostatic and polarizations. High-performance charging methods are critical for electret transducers. Unlike dielectric barrier discharge (DBD) charging, the soft X-ray charging method, with its strong penetration ability, has been widely used in electrets after packaging and has even been embedded in high-aspect-ratio structures (HARSs). However, the related charging model and the charging effect of the soft X-ray irradiation remain unclear. In this study, the charge carrier migration theory and the one-dimensional electrostatic model were employed to build the soft X-ray charging models. The influence of soft X-ray irradiation under deferent poling voltages was investigated theoretically and experimentally. The conducted space charge measurement based on a pulsed electro-acoustic (PEA) system with a soft X-ray generator revealed that soft X-ray charging can offer higher surface charge densities and piezoelectricity to cellular electrets under the critical poling voltage lower than twice the breakdown voltage.

In-Situ Growth of Graphene Films to Improve Sensing Performances.

Graphene films made by chemical vapor deposition (CVD) are a popular method to modify sensors by virtue of large-scale and reproducibility, but suffer from various surface contamination and structural defects induced during transfer procedures. In-situ growth of graphene films is proposed in this review article to improve sensing performance. Root causes of the surface contamination and structural defects are revealed with several common transfer methods. In-situ approaches are introduced and compared, growing graphene films with clean surfaces and few defects. This allows graphene film to display superior sensing performance for sensor applications. This work may reasonably be expected to offer a good avenue for synthesis of graphene films applicable for sensing applications.

Non-canonical phosphoglycerate dehydrogenase activity promotes liver cancer growth via mitochondrial translation and respiratory metabolism.

Phosphoglycerate dehydrogenase (PHGDH) is a key serine biosynthesis enzyme whose aberrant expression promotes various types of tumors. Recently, PHGDH has been found to have some non-canonical functions beyond serine biosynthesis, but its specific mechanisms in tumorigenesis remain unclear. Here, we show that PHGDH localizes to the inner mitochondrial membrane and promotes the translation of mitochondrial DNA (mtDNA)-encoded proteins in liver cancer cells. Mechanistically, we demonstrate that mitochondrial PHGDH directly interacts with adenine nucleotide translocase 2 (ANT2) and then recruits mitochondrial elongation factor G2 (mtEFG2) to promote mitochondrial ribosome recycling efficiency, thereby promoting mtDNA-encoded protein expression and subsequent mitochondrial respiration. Moreover, we show that treatment with a mitochondrial translation inhibitor or depletion of mtEFG2 diminishes PHGDH-mediated tumor growth. Collectively, our findings uncover a previously unappreciated function of PHGDH in tumorigenesis acting via promotion of mitochondrial translation and bioenergetics.

An Optimization Method for the Station Layout of a Microseismic Monitoring System in Underground Mine Engineering.

The layout of microseismic monitoring (MSM) station networks is very important to ensure the effectiveness of source location inversion; however, it is difficult to meet the complexity and mobility requirements of the technology in this new era. This paper proposes a network optimization method based on the geometric parameters of the proposed sensor-point database. First, according to the monitoring requirements and mine-working conditions, the overall proposed point database and model are built. Second, through the developed model, the proposed coverage area, envelope volume, effective coverage radius, and minimum energy level induction value are comprehensively calculated, and the evaluation reference index is constructed. Third, the effective maximum envelope volume is determined by taking the analyzed limit of monitoring induction energy level as the limit. Finally, the optimal design method is identified and applied to provide a sensor station layout network with the maximum energy efficiency. The method, defined as the S-V-E-R-V model, is verified by a comparison with the existing layout scheme and numerical simulation. The results show that the optimization method has strong practicability and efficiency, compared with the mine's layout following the current method. Simulation experiments show that the optimization effect of this method meets the mine's engineering requirements for the variability, intelligence, and high efficiency of the microseismic monitoring station network layout, and satisfies the needs of event identification and location dependent on the station network.

Isoquercetin alleviates sleep deprivation dependent hippocampal neurons damage by suppressing NLRP3-induced pyroptosis.

Purpose: Sleep deprivation (SD) leads to memory and cognitive impairment due to damage to the hippocampus. Isoquercetin possesses neuron-protective properties. Our study aimed to investigate the effects of isoquercetin on SD-induced hippocampal neurons damage and the underlying mechanism.Materials and methods: Herein, the cognitive competence was evaluated by Morris water maze test after SD. The morphology of the hippocampus was observed after Nissl staining. Moreover, the level of NLRP3 was detected by Immunofluorescent staining and western blot. In vitro study, pyroptosis was tested by TUNEL assay and flow cytometry. The levels of pyroptosis-related factors were measured by western blot.Results: The results indicated that isoquercetin improved spatial memory and prevented change of hippocampal neurons of SD mice. Moreover, SD upregulated NLRP3 level, which was downregulated by isoquercetin. Additionally, isoquercetin rescued the increase of pyroptosis and the upregulation of NLRP3, caspase-1, ASC, IL-1ß, IL-18, and GSDMD levels induced by LPS.Conclusions: In conclusion, isoquercetin improved learning and cognitive capability of SD mice via suppressing NLRP3-induced pyroptosis of hippocampal neurons cells, suggesting that isoquercetin might be an efficacious drug for memory disorders caused by SD.

Increased density and antagonistic allosteric interactions in A2AR-D2R heterocomplexes in extinction from cocaine use, lost in cue induced reinstatement of cocaine seeking.

Neurochemical studies were previously performed on the effects of a 10 day extinction learning from cocaine self-administration on D2R and A2AR recognition and D2R Gi/o coupling in the ventral striatum. In the present study biochemical receptor binding and proximity ligation assay were used to study possible changes in the allosteric receptor-receptor interactions and the density of the A2AR-D2R heterocomplexes in the ventral striatum (nucleus accumbens shell) in extinction from cocaine self-administration including cue induced reinstatement of cocaine seeking. A significant and clear-cut reduction of active lever pressing was observed in extinction on day 10 from cocaine use. In cue induced reinstatement of cocaine self-administration a significant return in active lever presses developed. In extinction, significant increases in the density of A2AR-D2R and D2R-Sigma1R heterocomplexes were observed in nucleus accumbens shell. In contrast, cue-induced reinstatement of cocaine seeking produced no significant changes in these heteroreceptor complexes of the nucleus accumbens shell. In the 3H raclopride/quinpirole competition binding experiments, the extinction led to a significant increase in the D2R Ki, High dissociation constant in the ventral striatum upon ex vivo exposure to CGS 21680 (100 nM), compared to the same exposure performed in membrane preparations from yoked saline rats. No significant changes in D2R Ki, High values were observed in membrane preparations from rats after cue-induced reinstatement of cocaine-seeking undergoing the same exposure ex vivo to CGS 21680 when compared with membrane preparations from yoked saline rats undergoing the same procedures. It seems likely that increased formation of A2AR-D2R and putative A2AR-D2R-Sigma1R heterocomplexes in the nucleus accumbens shell is part of the mechanism for the enhanced antagonistic allosteric A2AR-D2R interactions developed in extinction learning from cocaine. It reduces cocaine reward through reduced D2R function, and these inhibitory mechanisms are no longer in operation in cue induced reinstatement of cocaine seeking.

Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.

Global Wave Velocity Change Measurement of Rock Material by Full-Waveform Correlation.

Measuring accurate wave velocity change is a crucial step in damage assessment of building materials such as rock and concrete. The anisotropy caused by the generation of cracks in the damage process and the uncertainty of the damage level of these building materials make it difficult to obtain accurate wave velocity change. We propose a new method to measure the wave velocity change of anisotropic media at any damage level by full-waveform correlation. In this method, the anisotropy caused by the generation of cracks in the damage process is considered. The accuracy of the improved method is verified by numerical simulation and compared with the existing methods. Finally, the proposed method is applied to measure the wave velocity change in the damage process of rock under uniaxial compression. We monitor the failure process of rock by acoustic emission (AE) monitoring system. Compared with the AE ringing count, the result of damage evaluation obtained by the proposed method is more accurate than the other two methods in the stage of increasing rock heterogeneity. These results show that the proposed method is feasible in damage assessment of building materials such as rock and concrete.