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.

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.

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.

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.

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.

Tectorigenin enhances PDX1 expression and protects pancreatic ß-cells by activating ERK and reducing ER stress.

Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet ß-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to ß-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve ß-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for the PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in ß-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of ß-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet ß-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring ß-cell mass and islet size, respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD-impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet ß-cells both in vitro and in vivo.

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.

A New Algebraic Solution for Acoustic Emission Source Localization without Premeasuring Wave Velocity.

The technique of acoustic emission (AE) source localization is critical for studying material failure mechanism and predicting the position of potential hazards. Most existing positioning methods heavily depend on the premeasured wave velocity and are not suitable for complex engineering practices where the wave velocity changes dynamically. To reduce the influence of measurement error of wave velocity on location accuracy, this paper proposes a new algebraic solution for AE source localization without premeasuring wave velocity. In this method, the nonlinear TDOA equations are established and linearized by introducing two intermediate variables. Then, by minimizing the sum of squared residuals of the linear TDOA equations with respect to the AE source coordinate and two intermediate variables separately, the optimal algebraic solution of the AE source coordinate in the least squares sense is obtained. A pencil-lead breaks experiment is performed to validate the positioning effectiveness of the proposed method. The results show that the new method improves the positioning accuracy by more than 40% compared with two pre-existing methods, and the minimum positioning accuracy of the proposed method can reach 1.12 mm. Moreover, simulation tests are conducted to further verify the location performance of the proposed method under different TDOA errors and the number of sensors.

A Weighted Linear Least Squares Location Method of an Acoustic Emission Source without Measuring Wave Velocity.

The location of an acoustic emission (AE) source is crucial for predicting and controlling potential hazards. In this paper, a novel weighted linear least squares location method for AE sources without measuring wave velocity is proposed. First, the governing equations of each sensor are established according to the sensor coordinates and arrival times. Second, a mean reference equation is established by taking the mean of the squared governing equations. Third, the system of linear equations can be obtained based on the mean reference equation, and their residuals are estimated to obtain their weights. Finally, the AE source coordinate is obtained by weighting the linear equations and inserting the parameter constraint. The AE location method is verified by a pencil lead break experiment, and the results show that the locating accuracy of the proposed method is significantly higher than that of traditional methods. Furthermore, the simulation test proves that the proposed method also has a better performance (location accuracy and stability) than the traditional methods under any given scale of arrival errors.

A Closed-Form Method of Acoustic Emission Source Location for Velocity-Free System Using Complete TDOA Measurements.

A closed-form method of acoustic emission (AE) source location for a velocity-free system using complete time difference of arrival (TDOA) measurements is proposed in this paper. First, this method established the governing equation of unknown acoustic velocity for each sensor; then, the governing equations of each of the three sensors were transformed into a linear equation, which can form a system of linear equations with the complete TDOA measurements. Third, the least squares solutions of the AE source coordinate and acoustic velocity were separately solved by an orthogonal projection operator. The proposed method was verified by the pencil-lead break experiment, and the results showed that the location accuracy and stability of the proposed method were better than those of traditional methods. Moreover, a simulation test was carried out to investigate the influence of noise scales on the location accuracy, and the results further prove that the proposed method holds higher noise immunity than the traditional methods.

A2AR Transmembrane 2 Peptide Administration Disrupts the A2AR-A2AR Homoreceptor but Not the A2AR-D2R Heteroreceptor Complex: Lack of Actions on Rodent Cocaine Self-Administration.

It was previously demonstrated that rat adenosine A2AR transmembrane V peptide administration into the nucleus accumbens enhances cocaine self-administration through disruption of the A2AR-dopamine (D2R) heteroreceptor complex of this region. Unlike human A2AR transmembrane 4 (TM4) and 5 (TM5), A2AR TM2 did not interfere with the formation of the A2AR-D2R heteroreceptor complex in cellular models using BRET1 assay. A2AR TM2 was proposed to be part of the of the receptor interface of the A2AR homomer instead and was therefore tested in the current article for effects on rat cocaine self-administration using rat A2AR synthetic TM2 peptide bilaterally injected into the nucleus accumbens. The injected A2AR TM2 peptide failed to significantly counteract the inhibitory action of the A2AR agonist CGS 21680 (0.1 mg/Kg) on cocaine self-administration. In line with these results, the microinjected A2AR TM2 peptide did not reduce the number of proximity ligation assay blobs identifying A2AR-D2R heteroreceptor complexes in the nucleus accumbens. In contrast, the A2AR TM2 peptide significantly reduced the number of A2AR-A2AR homoreceptor complexes in the nucleus accumbens. As to effects on the receptor-receptor interactions in the A2AR-D2R heteroreceptor complexes, the A2AR TM2 peptide did not alter the significant increase in the D2R Ki, high values produced by the A2AR agonist CGS 21680 ex vivo in the ventral striatum. The results indicate that the accumbal A2AR-A2AR homomeric complexes are not involved in mediating the A2AR agonist-induced inhibition of cocaine self-administration.

20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol negatively regulates activation of STAT3 and ERK pathways and exhibits anti-cancer effects in HepG2 cells.

The pro-inflammatory cytokine interleukin 6 (IL-6), via activating its downstream JAK/STAT3 and Ras/ERK signaling pathways, is involved in cell growth, proliferation and anti-apoptotic activities in various malignancies. To screen inhibitors of IL-6 signaling, we constructed a STAT3 and ERK dual-pathway responsive luciferase reporter vector (Co.RE). Among several candidates, the natural compound 20(S)-25-methoxyl-dammarane-3ß, 12ß, 20-triol (25-OCH3-PPD, GS25) was identified to clearly inhibit the luciferase activity of Co.RE. GS25 was confirmed to indeed inhibit activation of both STAT3 and ERK pathways and expression of downstream target genes of IL-6, and to predominantly decrease the viability of HepG2 cells via induction of cell cycle arrest and apoptosis. Interestingly, GS25 showed preferential inhibition of HepG2 cell viability relative to normal liver L02 cells. Further investigation showed that GS25 could not induce apoptosis and block activation of STAT3 and ERK pathways in L02 cells as efficiently as in HepG2 cells, which may result in differential effects of GS25 on malignant and normal liver cells. In addition, GS25 was found to potently suppress the expression of endogenous STAT3 at a higher concentration and dramatically induce p38 phosphorylation in HepG2 cells, which could mediate its anti-cancer effects. Finally, we demonstrated that GS25 also inhibited tumor growth in HepG2 xenograft mice. Taken together, these findings indicate that GS25 elicits its anti-cancer effects on HepG2 cells through multiple mechanisms and has the potential to be used as an inhibitor of IL-6 signaling. Thus, GS25 may be developed as a treatment for hepatocarcinoma with low toxicity on normal liver tissues as well as other inflammation-associated diseases.

A comprehensive evaluation method for dust pollution: Digital image processing and deep learning approach.

Dust pollution poses a grave threat to both the environment and human health, especially in mining operations. To combat this issue, a novel evaluation method is proposed, integrating grayscale average (GA) analysis and deep learning (DL) in image classification. By utilizing a self-designed dust diffusion simulation system, 300 sample images were generated for analysis. The GA method establishes a correlation between grayscale average and dust mass, while incorporating fractal dimension (FD) enhances classification criteria. Both GA and DL methods were trained and compared, yielding promising results with a testing accuracy of 92.2 % and high precision, recall, and F1-score values. This approach not only demonstrates efficacy in classifying dust pollution but also presents a versatile solution applicable beyond mining to diverse dust-contaminated work environments. By combining image processing and deep learning, it offers an automated and reliable system for environmental monitoring, thereby enhancing safety standards and health outcomes in affected industries. Ultimately, this innovative method signifies a significant advancement towards mitigating dust pollution and ensuring sustainable industrial practices.

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.

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.

Lactylation: the novel histone modification influence on gene expression, protein function, and disease.

Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential "writers" and "erasers" responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.

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.

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.