Mechanism of epigallocatechin gallate in treating non-alcoholic fatty liver disease: Insights from network pharmacology and experimental validation.

To explore the therapeutic effects along with the molecular mechanisms of epigallocatechin gallate (EGCG) in non-alcoholic fatty liver disease (NAFLD) treatment using network pharmacology as well as animal experiments. Firstly, the Traditional Chinese Medicine (TCM) Systems Pharmacology Database was searched to identify the potential targets of EGCG. The DisGeNET Database was used to screen the potential targets of NAFLD. The GeneCards Database was searched to identify related genes involved in pyroptosis. Subsequently, the intersecting genes of EGCG targeting pyroptosis to regulate NAFLD were obtained using a Venn diagram. Simultaneously, the aforementioned intersecting genes were used to construct a drug-disease target protein-protein interaction (PPI) network. The DAVID database was adopted for Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The main pathway-target network was determined. Next, the potential mechanism of EGCG targeting pyroptosis to regulate NAFLD was investigated and validated through in vivo experiments. 626 potential targets of EGCG, 447 target genes of NAFLD, and 568 potential targets of pyroptosis were identified. The number of common targets between EGCG, NAFLD, and pyroptosis was 266. GO biological process items and 92 KEGG pathways were determined based on the analysis results. Animal experiments demonstrated that EGCG could ameliorate body weight, glucolipid metabolism, steatosis, and liver injury, enhance insulin sensitivity, and improve glucose tolerance in NAFLD mice through the classical pathway of pyroptosis. EGCG could effectively treat NAFLD through multiple targets and pathways. It was concluded that EGCG ameliorates hepatocyte steatosis, pyroptosis, dyslipidemia, and inflammation in NAFLD mice fed a high-fat diet (HFD), and the protective mechanism could be associated with the NLRP3-Caspase-1-GSDMD classical pyroptosis pathway.

Epigallocatechin gallate attenuated high glucose-induced pancreatic beta cell dysfunction by modulating DRP1-mediated mitochondrial apoptosis pathways.

Long-term exposure to hyperglycemic conditions leads to ß-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of ß-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus.

Experimental demonstration of constant amplitude modulation heterodyne interferometry.

In the space gravitational wave detection, numerous laser interferometer strategies have been proposed to reduce the complexity of traditional heterodyne interferometers. Previously, we proposed a novel interferometric strategy and simulated its effectiveness, called CAM (constant amplitude modulation) heterodyne interferometry. Compared with other methods, the CAM can introduce the OPT (optical pilot tone) for the common-mode noise rejection. In this paper, we present the first, to our knowledge, experimental verification of this technique. The experimental results indicate that OPT can successfully eliminate sampling jitter, enabling the corrected noise to meet the requirements of space gravitational wave detection. This provides a new approach for further optical optimization and noise elimination in the future.

Multi-frequency signal acquisition and phase measurement in space gravitational wave detection.

To enhance the accuracy of phase measurement and to prevent tracking errors, it is crucial to effectively read the multi-frequency signal in space gravitational wave detection. In this paper, a novel signal acquisition method called the multi-frequency acquisition algorithm is proposed and implemented. Different from the traditional single-frequency acquisition, the signal characteristics of amplitude and frequency are both considered to better distinguish different frequency components. A phasemeter integrated with the acquisition method and narrow-bandwidth digital phase-locked loop is constructed for the method test and verification. The results show that the multi-frequency acquisition unit can capture all the frequencies of an input signal in several milliseconds. The precision is better than ±200 Hz under a low SNR (signal-to-noise ratio) of 0 dB. The phase noise can reach 2 µrad/Hz1/2 in the frequency range of 0.1-1 Hz and satisfy the requirement of the space gravitational wave detection in all frequency ranges.

Design and Construction of the Optical Bench Interferometer for the Taiji Program.

A kind of full-function two-sided optical bench interferometer (OBI) is designed to meet the practical requirements of the Taiji Program for space gravitational wave detection. The main optical paths are arranged on the A-side for transmission and interference, and other optical paths and electronic devices are placed on the B-side. According to the design scheme, we successfully constructed two OBIs by using hydrogen-oxygen catalytic stress-free bonding technology. When the OBI is installed and adjusted, the position and Angle error of the interference beam are controlled within 30 µm and 50 µrad through the self-designed precision mechanical clamping mechanism and beam position measuring device. The built OBI was placed on the vibration isolation platform in the vacuum tank for the stability test. The test results show that the noise of the OBI is less than 10 pm/√Hz in the frequency band of 0.1 Hz to 1 Hz, which meets the noise budget requirements of the Taiji Pathfinder in the middle- and high-frequency band.

Using DWS Optical Readout to Improve the Sensitivity of Torsion Pendulum.

In space gravitational wave detection missions, a drag-free system is used to keep the test mass (TM) free-falling in an ultralow-noise environment. Ground verification experiments should be carried out to clarify the shielding and compensating capabilities of the system for multiple stray force noises. A hybrid apparatus was designed and analyzed based on the traditional torsion pendulum, and a technique for enhancing the sensitivity of the torsion pendulum system by employing the differential wavefront sensing (DWS) optical readout was proposed. The readout resolution experiment was then carried out on an optical bench that was designed and established. The results indicate that the angular resolution of the DWS signal in optical readout mode can reach the level of 10 nrad/Hz1/2 over the full measurement band. Compared with the autocollimator, the sensitivity of the torsional pendulum is noticeably improved, and the background noise is expected to reach 4.5 × 10-15 Nm/Hz1/2@10 mHz. This method could also be applied to future upgrades of similar systems.

Unsupervised Noise Reductions for Gravitational Reference Sensors or Accelerometers Based on the Noise2Noise Method.

Onboard electrostatic suspension inertial sensors are important applications for gravity satellites and space gravitational-wave detection missions, and it is important to suppress noise in the measurement signal. Due to the complex coupling between the working space environment and the satellite platform, the process of noise generation is extremely complex, and traditional noise modeling and subtraction methods have certain limitations. With the development of deep learning, applying it to high-precision inertial sensors to improve the signal-to-noise ratio is a practically meaningful task. Since there is a single noise sample and unknown true value in the measured data in orbit, odd-even sub-samplers and periodic sub-samplers are designed to process general signals and periodic signals, and adds reconstruction layers consisting of fully connected layers to the model. Experimental analysis and comparison are conducted based on simulation data, GRACE-FO acceleration data, and Taiji-1 acceleration data. The results show that the deep learning method is superior to traditional data smoothing processing solutions.

In vitro PCR verification that lysozyme inhibits nucleic acid replication and transcription.

Lysozyme can kill bacteria by its enzymatic activity or through a mechanism involving its cationic nature, which can facilitate electrostatic interactions with the viral capsid, the negatively charged parts of nucleic acids, and polymerase, so binding to nucleic acids may be another biological function of lysozyme. Here, PCR was used as a research tool to detect the effects of lysozyme on the replication and transcription of nucleic acids after treatment in different ways. We found that lysozyme and its hydrolysate can enter cells and inhibit PCR to varying degrees in vitro, and degraded lysozyme inhibited nucleic acid replication more effectively than intact lysozyme. The inhibition of lysozyme may be related to polymerase binding, and the sensitivity of different polymerases to lysozyme is inconsistent. Our findings provide a theoretical basis for further explaining the pharmacological effects of lysozyme, such as antibacterial, antiviral, anticancer, and immune regulatory activities, and directions for the development of new pharmacological effects of lysozyme and its metabolites.

Study on the Effect of Micro-Force Perturbations and Temperature Fluctuation on Interferometer for the Taiji Program.

To increase the interferometric measurement resolution in the Taiji program, we present a noise suppression method in this paper. Taking the specific micro-force perturbation and temperature fluctuation in the Taiji-1 interferometer as an example, we set up and experimentally verified the corresponding transfer function to quantify the effect of both noise sources on the interferometric results. Consistent results were obtained between the numerical and experimental results for the transfer function. It is instructive to eliminate the micro-force perturbations and temperature fluctuations during on-orbit interferometric measurement for as long as the acquisition of the force or temperature distribution of related surfaces and the corresponding transfer functions. This indicates that the method can be used for noise sensing and more in the field of noise elimination and measurement resolution improvement for future Taiji program interferometers.

A Formal Performance Evaluation Method for Customised Plug-and-Play Manufacturing Systems Using Coloured Petri Nets.

Recent technological advancements and the evolution of industrial manufacturing paradigms have substantially increased the complexity of product-specific production systems. To reduce the time cost of modelling and verification and to enhance the degree of uniformity in the modelling process of system components, this article presents a componentised framework for domain modelling and performance analysis based on the concept of "multi-granularity and multi-view" for a production line of personalised and customised products, for plug-and-play manufacturing processes to involving a large number of model input parameters. The coloured Petri net tool is utilised as a simulation tool for mapping domain models to computational models for simulation and performance evaluation. This paper presents a method for setting the input parameters of a production system when using WIP, through-put and cycle time as metrics. The results of the performance analysis demonstrate the applicability of the proposed framework and provide direction for the production line's layout design and scheduling strategy.

Constant amplitude modulation heterodyne interferometry.

Laser interferometer with picometer precision is a key technology in the space gravitational wave detection. Many interferometry strategies have been put forward for the multiple purposes in the past 10 yr. We propose a new interferometry method, called constant amplitude modulation (CAM) heterodyne interferometry. Differently, the CAM provides an optical pilot tone (OPT) for the noise correction theme. Compared with the analog pilot tone, the OPT can record and correct more noises, such as the analog to digital converter sampling jitter, the photodetector noise and the analog front-end noise. From the discussion, the modulated depth ϕmodulate=1.375 rad and the power ratio of the beam split n=0.432 are the best choice for the CAM-modulated parameter. Moreover, a simulated case has been implemented for the verification of the CAM strategy. Therefore, the CAM gives us another excellent choice in the optical design of the interferometer.

A low-noise analog frontend design for the Taiji phasemeter prototype.

The Taiji program plans to utilize the laser interferometer to measure the movement at the picometer level between free-floating test masses. As the phase readout equipment, the phasemeter needs to obtain the beat note with an accuracy of µrad/Hz. The main source of noise in the phasemeter is the analog frontend of the analog to digital converter. A self-designed phasemeter prototype with a low-noise analog frontend, which includes the theme of the pilot tone correction, has been developed and tested for the Taiji program in this Note. The experimental results show that the performance of the developed phasemeter can satisfy the Taiji sensitivity requirement in the whole frequency range. The sensitivity of the board can reach 0.5 µrad/Hz in the frequency range of 0.1-1 Hz. Therefore, the prototype gives us a good model for the fully functional Taiji phasemeter.

Laser acquisition experimental demonstration for space gravitational wave detection missions.

The laser acquisition-pointing technique is one of the most important techniques for space gravitational wave detection missions, like the Taiji program and the LISA (Laser Interferometer Space Antenna) program. The laser acquisition system suppresses the laser deviation angle to 1 µrad at the receiving aperture. Corresponding to 80 times of telescope magnification, the acquisition accuracy should reach 80 µrad at the acquisition camera. In order to verify the feasibility of the laser acquisition scheme, a laser acquisition ground simulation experimental system is designed and constructed. The experimental system simulates the actual acquisition process of the Taiji from three aspects: optical path, acquisition accuracy and acquisition scanning process. In the experiment, the coupling between the laser acquisition system and the laser pointing system is considered by introducing the DWS (Differential Wave-front Sensing) technique to calibrate the reference position of the acquisition camera and read out the acquisition precision. Due to limited beam propagation distance in the ground experiment, the in-flat top properties of the transmitting beam will greatly affect the acquisition precision. Based on the analysis of the influence, an improved acquisition ground simulation scheme is introduced. The experimental results indicate that the experimental system can achieve the acquisition accuracy of sub-10 µrad magnitude at the acquisition camera. The experimental system realizes methodological demonstration of the acquisition scheme. The results offer the experimental foundation and theoretical basis for the acquisition system of the Taiji/LISA program.

Automatic, high-speed, high-precision acquisition scheme with QPD for the Taiji program.

Most of the space gravitational wave detection missions, such as the Taiji program, use space-based laser interferometer to sense the gravitational waves. However, to obtain the interference signal, the inter-satellite laser acquisition scheme is firstly required to establish the laser link. Traditional acquisition sensors are CCD cameras, which cause a serious heating problem and call for high alignment precision. To avoid these questions, a high-speed, high-precision, fully automatic acquisition scheme with quadrant photodetectors (QPD) is proposed in this paper. Incoherent measurement method of the QPD is introduced to fulfill high-speed acquisition, while a dedicated imaging system is involved for automatic acquisition. Also, an improved differential power sensing (DPS) signal is developed. Combined with the down-sampling algorithm and the match filter algorithm, the acquisition scheme can achieve 1 µrad resolution with total scanning time less than 220 s.

EGCG Upregulates UCP3 Levels to Protect MIN6 Pancreatic Islet Cells from Interleukin-1ß-Induced Apoptosis.

OBJECTIVE: The protective effects of epigallocatechin gallate (EGCG) on interleukin-1ß (IL-1ß)-induced apoptosis were investigated in murine MIN6 pancreatic ß-cells. The role of uncoupling protein-3 (UCP3) signaling in this process was also explored. METHODS: After treatment with IL-1ß and EGCG, cells were collected and analyzed. Cell viability was measured using the CCK8 assay and the function of ß-cells was evaluated by analyzing insulin secretion. Detection of mitochondrial function in cells was performed by measuring mitochondrial membrane potential, the concentration of ATP and activity of ROS. Apoptosis was analyzed by Hochest33258 staining and flow cytometry. Expression levels of UCP3 were interrogated using immunohistochemistry, RT-PCR and Western blotting. RESULTS: Compared with the control group, IL-1ß treatment (20nM) for 24 h significantly decreased cell viability and insulin secretion, damaged mitochondrial function and increased ROS activity. Results also showed increased apoptosis and a decrease in UCP3 expression levels (p<0.01). However, treatment with low (1mM) or high (5mM) concentrations of EGCG significantly decreased IL-1ß-induced apoptosis (p<0.01), restored mitochondrial function and subsequently increased UCP3 levels in IL-1ß-induced ß-cells (p<0.01). CONCLUSION: These results suggest that EGCG protects against IL-1ß-induced mitochondrial injury and apoptosis in ß-cells through the up-regulation of UCP3.

Tilt-to-length noise coupled by wavefront errors in the interfering beams for the space measurement of gravitational waves.

The space-based gravitational wave detection programs, like the Laser Interferometer Space Antenna (LISA) or the Taiji program, aim to detect gravitational waves in space with a triangular constellation of three spacecraft. The unavoidable jitters of the spacecraft and the pointing will couple with the misalignment of the interfering beams into the longitudinal path length readout. This effect is called tilt-to-length (TTL) coupling, which is one of the keys to achieving the required measuring accuracy of 1pm/Hz. In terms of two phase definitions (the LISA Pathfinder (LPF) signal and the Average Phase (AP) signal), we implement the comprehensive theoretical analysis concerning the effect of aberrations on TTL coupling noise. In addition, we analytically derive that the proper lateral shift of the interfering beams relative to the detector can partly cancel out the TTL noise coupled with aberrations, especially coma and trefoil aberrations for the AP signal. Based on the above results, the meaningful guidance can be provided for the design and construction of the optical system in LISA or Taiji.

High-precision laser spot center positioning method for weak light conditions.

In the acquisition stage of many space applications, such as the Taiji program, the spot center of weak laser light must be accurately determined. Under weak light conditions, the precision of most traditional positioning methods is greatly affected. In this paper, we present a high-precision laser spot center positioning method based on the theoretical analysis of influence factors of precision. It is shown through experimental study that the method's precision can fulfill the requirement of the Taiji program.

Kinetic analysis of the weak affinity interaction between tris and lysozyme.

The biosensor based on total internal reflection imaging ellipsometry (TIRIE), regarded as an automotive real-time research approach for biomolecular interaction, is introduced to analyze the kinetic process of the weak interaction between tris and lysozyme. The experiment is performed by delivering lysozyme solution diluted to different concentrations to the biosensor substrate interface immobilized with tris. By applying pseudo-first-order interaction kinetics model, we are able to obtain the kinetic parameters from fitting experimental data. The calculated association rate constant and dissociation rate constant of tris and lysozyme interaction are in 10(-2) mol(-1) s(-1) and 10(3)s(-1) magnitude, respectively. To further improve TIRIE's ability for kinetically characterizing biomolecular interaction, a theoretical method to deduce associate rate constant before experiment is proposed.

Methodological demonstration of laser beam pointing control for space gravitational wave detection missions.

In space laser interferometer gravitational wave (G.W.) detection missions, the stability of the laser beam pointing direction has to be kept at 10 nrad/√Hz. Otherwise, the beam pointing jitter noise will dominate the noise budget and make the detection of G.W. impossible. Disturbed by the residue non-conservative forces, the fluctuation of the laser beam pointing direction could be a few µrad/√Hz at frequencies from 0.1 mHz to 10 Hz. Therefore, the laser beam pointing control system is an essential requirement for those space G.W. detection missions. An on-ground test of such beam pointing control system is performed, where the Differential Wave-front Sensing technique is used to sense the beams pointing jitter. An active controlled steering mirror is employed to adjust the beam pointing direction to compensate the jitter. The experimental result shows that the pointing control system can be used for very large dynamic range up to 5 µrad. At the interested frequencies of space G.W. detection missions, between 1 mHz and 1 Hz, beam pointing stability of 6 nrad/√Hz is achieved.

The evaluation of phasemeter prototype performance for the space gravitational waves detection.

Heterodyne laser interferometry is considered as the most promising readout scheme for future space gravitational wave detection missions, in which the gravitational wave signals disguise as small phase variances within the heterodyne beat note. This makes the phasemeter, which extracts the phase information from the beat note, the key device to this system. In this paper, a prototype of phasemeter based on digital phase-locked loop technology is developed, and the major noise sources which may contribute to the noise spectra density are analyzed in detail. Two experiments are also carried out to evaluate the performance of the phasemeter prototype. The results show that the sensitivity is achieved 2π µrad/√Hz in the frequency range of 0.04 Hz-10 Hz. Due to the effect of thermal drift, the noise obviously increases with the frequencies down to 0.1 mHz.