Promoter replication of grape MYB transcription factor is associated with a new red flesh phenotype.

KEY MESSAGE: In our study, we discovered a fragment duplication autoregulation mechanism in 'ZS-HY', which may be the reason for the phenotype of red foliage and red flesh in grapes. In grapes, MYBA1 and MYBA2 are the main genetic factors responsible for skin coloration which are located at the color loci on chromosome 2, but the exact genes responsible for color have not been identified in the flesh. We used a new teinturier grape germplasm 'ZhongShan-HongYu' (ZS-HY) which accumulate anthocyanin both in skin and flesh as experimental materials. All tissues of 'ZS-HY' contained cyanidin 3-O-(6″-p-coumaroyl glucoside), and pelargonidins were detected in skin, flesh, and tendril. Through gene expression analysis at different stage of flesh, significant differences in the expression levels of VvMYBA1 were found. Gene amplification analysis showed that the VvMYBA1 promoter is composed of two alleles, VvMYBA1a and 'VvMYBA1c-like'. An insertion of a 408 bp repetitive fragment was detected in the allele 'VvMYBA1c-like'. In this process, we found the 408 bp repetitive fragment was co-segregated with red flesh and foliage phenotype. Our results revealed that the 408 bp fragment replication insertion in promoter of 'VvMYBA1c-like' was the target of its protein, and the number of repeat fragments was related to the increase of trans-activation of VvMYBA1 protein. The activation of promoter by VvMYBA1 was enhanced by the addition of VvMYC1. In addition, VvMYBA1 interacted with VvMYC1 to promote the expression of VvGT1 and VvGST4 genes in 'ZS-HY'. The discovery of this mutation event provides new insights into the regulation of VvMYBA1 on anthocyanin accumulation in red-fleshed grape, which is of great significance for molecular breeding of red-fleshed table grapes.

SR-BI as a target of natural products and its significance in cancer.

Scavenger receptor class B type I (SR-BI) protein is an integral membrane glycoprotein. SR-BI is emerging as a multifunctional protein, which regulates autophagy, efferocytosis, cell survival and inflammation. It is well known that SR-BI plays a critical role in lipoprotein metabolism by mediating cholesteryl esters selective uptake and the bi-directional flux of free cholesterol. Recently, SR-BI has also been identified as a potential marker for cancer diagnosis, prognosis, or even a treatment target. Natural products are a promising source for the discovery of new drug leads. Multiple natural products were identified to regulate SR-BI protein expression. There are still a number of challenges in modulating SR-BI expression in cancer and in using natural products for modulation of such protein expression. In this review, our purpose is to discuss the relationship between SR-BI protein and cancer, and the molecular mechanisms regulating SR-BI expression, as well as to provide an overview of natural products that regulate SR-BI expression.

Qualitative and quantitative method for quality control of Itea ilicifolia based on antioxidant Q-markers.

Itea ilicifolia Oliv is a folk medicine with antioxidant potential. In this study, the fingerprints of 14 batches of I. ilicifolia were established by HPLC with 17 common peaks. The similarities evaluated by Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia (version 2012) were >0.89. Ten compounds were identified with definite structures by comparing the retention time and characteristic UV spectral pattern with those of reference substances. The antioxidant capacities of 14 batches of I. ilicifolia were evaluated based on O2 ·- , DPPH and ABTS·+ radical scavenging assays in combination with ferric reducing antioxidant power assay. Via multivariate statistical analyses of gray relation analysis, bivariate correlation analysis and partial least squares regression analysis, a study on the spectrum-effect relationship was then performed to screen eight peaks as the antioxidant Q-markers of I. ilicifolia. The contents of representative antioxidant Q-markers (isoorientin, orientin, vitexin, isovitexin and iteafuranal A) in samples were accurately determined to be 0.054-0.118%, 0.034-0.080%, 0.018-0.055%, 0.031-0.091% and 0.033-0.140%, respectively. The qualitative and quantitative analytical method based on Q-markers helps to control the antioxidant quality of I. ilicifolia, which will lay the foundation to promote the rational utilization of I. ilicifolia in curing diseases related to oxidative stress.

Discovery of 2-(isoxazol-5-yl)phenyl 3,4-dihydroxybenzoate as a potential inhibitor for the Wnt/ß-catenin pathway.

Carnosic acid could disrupt the ß-catenin/BCL9 protein-protein interaction and inhibit ß-catenin dependent transcription, thereby reduce the incidence of colorectal cancer induced by abnormal activation of Wnt/ß-catenin signalling pathway. However, its activity was weak (IC50 for SW480: 28.2 ± 2.05 µM) and total synthesis was difficult. During the structural simplification of natural products, S0 was revealed to be the basic pharmacophore of carnosic acid. Subsequent structural optimization of S0 led to the discovery of S11 as a possible anticancer agent with prominent proliferation inhibition effect (IC50 for SW480: 9.56 ± 0.91 µM) and best selectivity index (SI = 3.0) against Wnt hyperactive cancer cells. Futher mechanism investigation through TOP/FOP dual luciferase reporter assay, immunofluorescence, co-immunoprecipitation, microscale thermophoresis, downstream oncoprotein expression and cell apoptosis showed that compound S11 could significantly inhibit the proliferation of SW480 cells via obvioudsly decreasing the nucleus translocation of ß-catenin and effectively disrupting ß-catenin/BCL9 protein-protein interaction. Additionally, cell migration, molecule docking, in vitro stability and solubility assays were also conducted. Overall, S11 was worthy of in-depth study as a potential inhibitor for the Wnt/ß-catenin pathway and its discovery also proved that the structural simplification of natural products was still one of the effective methods to find new lead compounds or candidate drugs.

Genome-Wide Identification of Glutathione S-Transferase and Expression Analysis in Response to Anthocyanin Transport in the Flesh of the New Teinturier Grape Germplasm 'Zhongshan-HongYu'.

Anthocyanins are synthesized in the endoplasmic reticulum and then transported to the vacuole in plants. Glutathione S-transferases (GSTs) are thought to play a key role in anthocyanin transport. To clarify the mechanism of GST genes in the accumulation and transport of anthocyanin in the early fruit stage, we analyzed and characterized the GST family in the flesh of 'Zhongshan-HongYu' (ZS-HY) based on the transcriptome. In this study, the 92 GST genes identified through a comprehensive bioinformatics analysis were unevenly present in all chromosomes of grapes, except chromosomes 3, 9 and 10. Through the analysis of the chromosomal location, gene structure, conserved domains, phylogenetic relationships and cis-acting elements of GST family genes, the phylogenetic tree divided the GST genes into 9 subfamilies. Eighteen GST genes were screened and identified from grape berries via a transcriptome sequencing analysis, of which 4 belonged to the phi subfamily and 14 to the tau subfamily, and the expression levels of these GST genes were not tissue-specific. The phylogenetic analysis indicated that VvGST4 was closely related to PhAN9 and AtTT19. This study provides a foundation for the analysis of the GST gene family and insight into the roles of GSTs in grape anthocyanin transport.

Insights into the Inhibitory Mechanism of Viniferifuran on Xanthine Oxidase by Multiple Spectroscopic Techniques and Molecular Docking.

Viniferifuran was investigated for its potential to inhibit the activity of xanthine oxidase (XO), a key enzyme catalyzing xanthine to uric acid. An enzyme kinetics analysis showed that viniferifuran possessed a strong inhibition on XO in a typical anti-competitive manner with an IC50 value of 12.32 µM (IC50 for the first-line clinical drug allopurinol: 29.72 µM). FT-IR and CD data analyses showed that viniferifuran could induce a conformational change of XO with a decrease in the α-helix and increases in the ß-sheet, ß-turn, and random coil structures. A molecular docking analysis revealed that viniferifuran bound to the amino acid residues located within the activity cavity of XO by a strong hydrophobic interaction (for Ser1214, Val1011, Phe914, Phe1009, Leu1014, and Phe649) and hydrogen bonding (for Asn768, Ser876, and Tyr735). These findings suggested that viniferifuran might be a promising XO inhibitor with a favorable mechanism of action.

Small Molecular Drug Screening Based on Clinical Therapeutic Effect.

Virtual screening can significantly save experimental time and costs for early drug discovery. Drug multi-classification can speed up virtual screening and quickly predict the most likely class for a drug. In this study, 1019 drug molecules with actual therapeutic effects are collected from multiple databases and documents, and molecular sets are grouped according to therapeutic effect and mechanism of action. Molecular descriptors and molecular fingerprints are obtained through SMILES to quantify molecular structures. After using the Kennard-Stone method to divide the data set, a better combination can be obtained by comparing the combined results of five classification algorithms and a fusion method. Furthermore, for a specific data set, the model with the best performance is used to predict the validation data set. The test set shows that prediction accuracy can reach 0.862 and kappa coefficient can reach 0.808. The highest classification accuracy of the validation set is 0.873. The more reliable molecular set has been found, which could be used to predict potential attributes of unknown drug compounds and even to discover new use for old drugs. We hope this research can provide a reference for virtual screening of multiple classes of drugs at the same time in the future.

[Study on UIPLC-DAD fingerprint of Disporum cantoniense].

OBJECTIVE: To establish an UHPLC-DAD fingerprint of 30 batches of Miao medicine Disporum cantoniense from Guizhou, and to provide a theoretical evidence to evaluate its quality. METHODS: The analysis was carried out on an Agilent Eclipse ZOR-BAX Plus C18 (100 mm x 2. 1 mm, 1. 8 µm) column with a mobile phase consisting of acetonitrile-water(containing 0. 1% formic acid) with gradient elution, and the flow rate was 0. 3 mL/min. The column temperature was set at 40 °C and UV detection wavelength was set at 290 nm. The sample injection volume was 3 µL. The similarity evaluation and principal component analysis(PCA) of these fingerprints were carried out. RESULTS: The UHPLC-DAD fingerprint was established and compared by 30 batches of samples similarity with 12 common peaks and 3 peaks were identified. The similarities of 30 batches of Disporum cantoniense were between 0. 766 and 0. 994. The principal component analysis showed that compounds 1 and 12 were representative for the fingerprint. CONCLUSION: The method is accurate and credible,which can be used for identification and quality control of Disporum cantoniense.

Parallel Grooved Microstructure Manufacturing on the Surface of Si3N4 Ceramics by Femtosecond Laser.

Machining special microstructures on the surface of silicon nitride ceramics helps improve their service performance. However, the high brittleness and low fracture toughness of silicon nitride ceramics make it extremely difficult to machine microstructures on their surface. In this study, a femtosecond laser is used to machine parallel grooved microstructures on the surface of silicon nitride ceramics. The effects of the laser polarization angle, laser single pulse energy, scanning line spacing, and laser scan numbers on the surface morphology and geometric characteristics of grooved microstructures are researched. It is found that a greater angle between the direction of the scanning path and laser polarization is helpful to obtain a smoother surface. As the single pulse energy increases, debris and irregular surface structures will emerge. Increasing the laser scan line spacing leads to clearer and more defined parallel grooved microstructures. The groove depth increases with the increase in the scan numbers. However, when a certain number of scans is reached, the depth will not increase further. This study serves as a valuable research foundation for the femtosecond laser processing of silicon nitride ceramic materials.

Data-Driven Battery Characterization and Prognosis: Recent Progress, Challenges, and Prospects.

Battery characterization and prognosis are essential for analyzing underlying electrochemical mechanisms and ensuring safe operation, especially with the assistance of superior data-driven artificial intelligence systems. This review provides a unique perspective on recent progress in data-driven battery characterization and prognosis methods. First, recent informative image characterization and impedance spectrum as well as high-throughput screening approaches on revealing battery electrochemical mechanisms at multiple scales are summarized. Thereafter, battery prognosis tasks and strategies are described, with the comparison of various physics-informed modeling strategies. Considering unlocking mechanisms from tremendous battery data, the dominant role of physics-informed interpretable learning in accelerating energy device development is presented. Finally, challenges and prospects on data-driven characterization and prognosis are discussed toward accelerating energy device development with much-enhanced electrochemical transparency and generalization. This review is hoped to supply new ideas and inspirations to the next-generation battery development.

Efficacy of ornidazole for pericoronitis: a meta-analysis and systematic review.

Introduction: Timely and effective treatments of pericoronitis are very important. We aimed to evaluate the role of ornidazole in the treatment of pericoronitis, to provide insights for clinical pericoronitis treatment. Material and methods: The PubMed, Clinical trials, EMBASE, Science Direct, Cochrane Library, China National Knowledge Infrastructure (CNKI), Weipu and Wanfang databases were searched to find randomized controlled trials (RCTs) of ornidazole in the treatment of pericoronitis from the establishment of the database to March 15, 2023. Review Manager 5.3 software was used for meta-analysis. Results: A total of 16 RCTs involving 2004 patients were included. The results of the meta-analysis showed that the effective rate of ornidazole treatment was significantly higher than that of the routine treatment group (RR = 1.22, 95% CI (1.15, 1.29), p < 0.001). Ornidazole treatment was beneficial to reduce the oral bacterial density (MD = -26.13, 95% CI (-32.08, -21.51)), time to pain disappearance (MD = -0.64, 95% CI (-0.92, -0.17)) and time to disappearance of redness and swelling of the teeth crown (MD = -1.45, 95% CI (-2.43, -1.01)) compared to the routine treatment (all p = 0.05). No publication bias was found by the funnel plots and Egger test (p = 0.206). Conclusions: Ornidazole is effective in the treatment of pericoronitis, with more advantages. Still, the effects and safety of ornidazole in the treatment of pericoronitis need to be evaluated by more high-quality RCTs with larger sample sizes.

Blockade of pre- and post-synaptic GABAB receptors in the anteroventral bed nucleus of stria terminalis produces anxiolytic-like and anxiety-like effects in parkinsonian rats respectively.

The anteroventral bed nucleus of stria terminalis (avBNST) is a limbic forebrain region involved in the regulation of anxiety, and expresses GABAB receptors, which are located at both pre- and post-synaptic sites. However, it is unclear how blockade of these receptors affects anxiety-like behaviors, particularly in Parkinson's disease (PD)-related anxiety. In the present study, unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, and increased GABA release and decreased glutamate release in the avBNST, as well as decreased level of dopamine (DA) in the basolateral amygdala (BLA). Intra-avBNST injection of pre-synaptic GABAB receptor antagonist CGP36216 produced anxiolytic-like effects, while the injection of post-synaptic GABAB receptor antagonist CGP35348 induced anxiety-like responses in both sham and 6-OHDA rats. Intra-avBNST injection of CGP36216 inhibited the GABAergic neurons and increased GABA/glutamate ratio in the avBNST and increased levels of DA and serotonin (5-HT) in the BLA; conversely, CGP35348 produced opposite effects on the firing activity of avBNST GABAergic neurons and levels of the neurotransmitters in the avBNST and BLA. Moreover, the doses of the antagonists producing significant behavioral effects in 6-OHDA rats were lower than those in sham rats, and the duration of action of the antagonists on the firing rate of the neurons and release of the neurotransmitters was prolonged in 6-OHDA rats. Altogether, these findings suggest that pre- and post-synaptic GABAB receptors in the avBNST are implicated in PD-related anxiety-like behaviors, and degeneration of the nigrostriatal pathway enhances functions and/or upregulates expression of these receptors.

Lesions of the lateral habenula excite dopamine neurons in the ventral tegmental area and serotonin neurons in the dorsal raphe nuclei in hemiparkinsonian rats.

The lateral habenula (LHb) projects to the ventral tegmental area (VTA) and dorsal raphe nuclei (DRN) that deliver dopamine (DA) and serotonin (5-HT) to cortical and limbic regions such as the medial prefrontal cortex (mPFC), hippocampus and basolateral amygdala (BLA). Dysfunctions of VTA-related mesocorticolimbic dopaminergic and DRN-related serotonergic systems contribute to non-motor symptoms in Parkinson's disease (PD). However, how the LHb affects the VTA and DRN in PD remains unclear. Here, we used electrophysiological and neurochemical approaches to explore the effects of LHb lesions on the firing activity of VTA and DRN neurons, as well as the levels of DA and 5-HT in related brain regions in unilateral 6-hydroxydopamie (6-OHDA)-induced PD rats. We found that compared to sham lesions, lesions of the LHb increased the firing rate of DA neurons in the VTA and 5-HT neurons in the DRN, but decreased the firing rate of GABAergic neurons in the same nucleus. In addition, lesions of the LHb increased the levels of DA and 5-HT in the mPFC, ventral hippocampus and BLA compared to sham lesions. These findings suggest that lesions of the LHb enhance the activity of mesocorticolimbic dopaminergic and serotonergic systems in PD.

A novel fluorescence probe for ultrafast detection of SO2 derivatives/biogenic amines and its multi-application: Detecting food and fish freshness, fluorescent dye and bioimaging.

In this study, we have effectively prepared a novel fluorescent probe named HDXM based on benzopyran derivatives for the ultrafast detection (within 3 s) of SO2 derivatives or biogenic amines. HDXM showed a noticeable color change after the addition of SO2 derivatives (from purple to colorless) or biogenic amines (from purple to blue), indicating that HDXM can identify two analytes with the naked eye. It is worth noting that HDXM can be used to detect SO2 derivatives in actual sugar samples, and to image HSO3-/SO32- in living cells. More importantly, sensing labels (HDXM-loaded filter paper or agarose hydrogel) enable real-time visual monitoring of salmon freshness through colorimetric and fluorescence dual channels. Compared with the Chinese national standard method, the sensing label is an effective tool for evaluating the freshness of fish. Benefiting from its excellent solubility and fluorescence performance, HDXM can be used as a versatile fluorescent material in various applications, including flexible films, glass coatings, impregnating dyes, printing, and fingerprint ink. HDXM is expected to be a promising and valuable multifunctional tool for food safety and fluorescent materials.

Advances in nanodisc platforms for membrane protein purification.

Membrane scaffold protein nanodiscs (MSPNDs) are an invaluable tool for improving purified membrane protein (MP) stability and activity compared to traditional micellar methods, thus enabling an increase in high-resolution MP structures, particularly in concert with cryogenic electron microscopy (cryo-EM) approaches. In this review we highlight recent advances and breakthroughs in MSPND methodology and applications. We also introduce and discuss saposin-lipoprotein nanoparticles (salipros) and copolymer nanodiscs which have recently emerged as authentic MSPND alternatives. We compare the advantages and disadvantages of MSPNDs, salipros, and copolymer nanodisc technologies to highlight potential opportunities for using each platform for MP purification and characterization.

Cathelicidin LL-37 promotes EMT, migration and metastasis of hepatocellular carcinoma cells in vitro and mouse model.

The effect of cathelicidin hCAP18/LL-37 in hepatocellular carcinoma (HCC) metastasis remains unclear. Here, we confirmed that LL-37 expression enhanced endothelial-mesenchymal transition (EMT), migration and invasion in HCC cells. And the HER2/EGFR-MAPK/ERK signal participated in the process above. More frequent lung metastases were observed in an LL-37-overexpressing hematogenous metastasis model. Interestingly, 1,25(OH)2D3 together with si-LL-37 significantly enhanced 1,25(OH)2D3-induced inhibition of migration and invasion in PLC/PRF-5 cells, and also enhanced reversion of the EMT process. Therefore, LL-37 is involved in HCC metastases, and may act as an important factor to attenuate the inhibitory activity of 1,25(OH)2D3 on HCC metastasis. Targeting hCAP18/LL-37 may offer a potential strategy to improve the anticancer activity of 1,25(OH)2D3 in HCC therapy.

The α1 and γ2 subunit-containing GABAA receptor-mediated inhibitory transmission in the anteroventral bed nucleus of stria terminalis is involved in the regulation of anxiety in rats with substantia nigra lesions.

The anteroventral bed nucleus of the stria terminalis (avBNST) is widely acknowledged as a key brain structure that regulates negative emotional states, such as anxiety. At present, it is still unclear whether GABAA receptor-mediated inhibitory transmission in the avBNST is involved in Parkinson's disease (PD)-related anxiety. In this study, unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) in rats induced anxiety-like behaviors, increased GABA synthesis and release, and upregulated expression of GABAA receptor subunits in the avBNST, as well as decreased level of dopamine (DA) in the basolateral amygdala (BLA). In both sham and 6-OHDA rats, intra-avBNST injection of GABAA receptor agonist muscimol induced the following changes: (i) anxiolytic-like responses, (ii) inhibition of the firing activity of GABAergic neurons in the avBNST, (iii) excitation of dopaminergic neurons in the ventral tegmental area (VTA) and serotonergic neurons in the dorsal raphe nucleus (DRN), and (iv) increase of DA and 5-HT release in the BLA, whereas antagonist bicuculline induced the opposite effects. Collectively, these findings suggest that degeneration of the nigrostriatal pathway enhances GABAA receptor-mediated inhibitory transmission in the avBNST, which is involved in PD-related anxiety. Further, activation and blockade of avBNST GABAA receptors affect the firing activity of VTA dopaminergic and DRN serotonergic neurons, and then change release of BLA DA and 5-HT, thereby regulating anxiety-like behaviors.

Anthocyanin accumulation in grape berry flesh is associated with an alternative splicing variant of VvMYBA1.

Anthocyanins are flavonoids that contribute to the color of grape berries and are an essential component of grape berry and wine quality. Anthocyanin accumulation in grape berries is dependent on the coordinated expression of genes encoding enzymes in the anthocyanin pathway that are principally regulated at the transcriptional level, with VvMYBA1 as the main transcriptional regulator in grapes. Alternative splicing (AS) events in VvMYBA1, however, have not been examined. In the present study, VvMYBA1-L, an AS variant of VvMYBA1, was identified in 'ZhongShan-Hong' (ZS-H) and its offspring. The AS variant is characterized by a deletion in the third exon of the open reading frame (ORF) of VvMYBA1-L, resulting in the early termination of the encoded protein. Overexpression of VvMYBA1-L in grape berries resulted in delayed flesh coloration and ectopic overexpression of VvMYBA1-L in tobacco inhibited the coloration of petals. Yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays revealed that VvMYBA1-L interacts with VvMYBA1. Dual luciferase assays indicated that co-infiltration of VvMYC1 and VvMYBA1 significantly activated the promoter regulated expression of VvCHS3, VvDFR, VvUFGT, and VvF3H. In the presence of VvMYBA1-L, however, the induction effect of VvMYBA1 on the indicated promoters was significantly inhibited. Our findings provide insight into the essential role of VvMYBA1 and its variant, VvMYBA1-L, in regulating anthocyanin accumulation in grape berry flesh.

Comparing the separation performance of poly(ethyleneimine) embedded butyric and octanoic acid based chromatographic stationary phases.

Poly(ethyleneimine) (PEI) modified silica spheres were used to graft butyric acid and octanoic acid onto their surfaces, forming two stationary phases named Sil-PEI-BAD and Sil-PEI-CAD, respectively. Characterized methods including fourier transform infrared spectroscopy (FT-IR), elemental analysis (EA) and thermogravimetric analysis (TGA) were utilized to determine the successful synthesis of these two stationary phase materials. The chromatographic performance of these two stationary phases was analyzed with hydrophobic and hydrophilic compounds as analytes. Compared with Sil-PEI-CAD column, Sil-PEI-BAD column was more effective in separating hydrophilic compounds including nucleosides, alkaloids and vitamins. Hydrophobic substances including polycyclic aromatic hydrocarbons (PAHs) and alkylbenzenes obtained excellent separation results on Sil-PEI-CAD column than Sil-PEI-BAD column. Additionally, according to the separation of phenols, Sil-PEI-CAD column can be used in HILIC/RPLC mixed-mode. The results showed that the properties and retention mechanisms of the prepared stationary phases depended on the length of the alkyl chains bonded on the silica surface.

Observation and research of deep underground multi-physical fields-Huainan -848 m deep experiment.

Compared with the surface, the deep environment has the advantages of allowing "super-quiet and ultra-clean"-geophysical field observation with low vibration noise and little electromagnetic interference, which are conducive to therealization of long-term and high-precision observation of multi-physical fields, thus enabling the solution of a series of geoscience problems. In the Panyidong Coal Mine, where there are extensive underground tunnels at the depth of 848 m belowsea level, we carried out the first deep-underground geophysical observations, including radioactivity, gravity, magnetic, magne-totelluric, background vibration and six-component seismic observations. We concluded from these measurements that (1) the background of deep subsurface gravity noise in the long-period frequency band less than 2 Hz is nearly two orders ofmagnitude weaker than that in the surface observation environment; (2) the underground electric field is obviously weaker thanthe surface electric field, and the relatively high frequency of the underground field, greater than 1 Hz, is more than two orders of magnitude weaker than that of the surface electric field; the east-west magnetic field underground is approximately the same asthat at the surface; the relatively high-frequency north-south magnetic field underground, below 10 Hz, is at least one order ofmagnitude lower than that at the surface, showing that the underground has a clean electromagnetic environment; (3) in additionto the high-frequency and single-frequency noises introduced by underground human activities, the deep underground spacehas a sig-nificantly lower background vibration noise than the surface, which is very beneficial to the detection of weakearthquake and gravity signals; and (4) the underground roadway support system built with ferromagnetic material interferesthe geomagnetic field. We also found that for deep observation in the "ultra-quiet and ultra-clean" environment, the existinggeophysical equipment and observation technology have problems of poor adaptability and insufficient precision as well asdata cleaning problems, such as the effective separation of the signal and noise of deep observation data. It is also urgent tointerpret and comprehensively utilize these high-precision multi-physics observation data. Electronic Supplementary Material: Supplementary material is available in the online version of this article at 10.1007/s11430-022-9998-2.