Progress in biological and medical research in the deep underground: an update.

As the growing population of individuals residing or working in deep underground spaces for prolonged periods, it has become imperative to understand the influence of factors in the deep underground environment (DUGE) on living systems. Heping Xie has conceptualized the concept of deep underground medicine to identify factors in the DUGE that can have either detrimental or beneficial effects on human health. Over the past few years, an increasing number of studies have explored the molecular mechanisms that underlie the biological impacts of factors in the DUGE on model organisms and humans. Here, we present a summary of the present landscape of biological and medical research conducted in deep underground laboratories and propose promising avenues for future investigations in this field. Most research demonstrates that low background radiation can trigger a stress response and affect the growth, organelles, oxidative stress, defense capacity, and metabolism of cells. Studies show that residing and/or working in the DUGE has detrimental effects on human health. Employees working in deep mines suffer from intense discomfort caused by high temperature and humidity, which increase with depth, and experience fatigue and sleep disturbance. The negative impacts of the DUGE on human health may be induced by changes in the metabolism of specific amino acids; however, the cellular pathways remain to be elucidated. Biological and medical research must continue in deep underground laboratories and mines to guarantee the safe probing of uncharted depths as humans utilize the deep underground space.

Experimental Study on the Damage Characteristics and Acoustic Properties of Red Sandstone with Different Water Contents under Microwave Radiation.

Rock breaking is one of the most basic issues in deep underground engineering. Water plays an important role in the rock response under microwave radiation. Consequently, microwave radiation experiments using red sandstone with different water contents were conducted. The damage characteristics and ultrasonic properties of red sandstone after microwave radiation were primarily investigated, and the representative conclusions were drawn as follows: With the increase in water content, the time of complete formation of the rupture surface of the rock sample gradually decreased, and the decreasing range gradually increased. When the fracture surface is completely formed, the samples with a higher water content have more powdery rock cuttings and less surface roughness. The damage degree of the samples does not increase significantly with the increase in the water content when the sample is radiated at the same time. As the microwave radiation time is increased, the damage degree of the sample will increase significantly. Through the ultrasonic velocity test, it can be suggested that the sample exhibits obvious zonal damage characteristics under the action of a microwave. Generally speaking, it is a very effective means of improving the degree of microwave attenuation of the rock by increasing the water content of the rock mass.

Transcriptome analysis of well-differentiated laryngeal squamous cell carcinoma cells in below-background environment.

Background: Preliminary research has shown an inhibited growth rate of well-differentiated laryngeal squamous cell carcinoma cells (FD-LSC-1) in below-background radiation (BBR), but how the cells respond to this environmental stress and the potential mechanisms are yet unknown. The current study aimed to reveal the molecular differences in cells grown under BBR conditions and normal radiation at the transcriptional level. Methods: The expression profiles between FD-LSC-1 cells grown in a deep underground laboratory and above ground laboratory collected on day 4 were investigated by whole-transcriptome analysis, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). Functional analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were then implemented for differentially expressed (DE) mRNAs and target genes of lncRNAs and circRNAs. Co-expression levels and the Bayesian network of DE genes were subsequently constructed, and the reliability of expression patterns were validated by quantitative real-time polymerase chain reaction (PCR). Results: The study identified a total of 671 mRNAs, 286 lncRNAs, 489 circRNAs, and 6 miRNAs as significantly expressed in response to the environmental stress. The GO annotations regarding the biological processes category were mainly biological regulation, metabolic process, response to stimulus, cell cycle, and modification process. The KEGG enrichment analysis indicated that TGF-ß and Hippo signaling played a crucial role in the transcriptional regulation of FD-LSC-1 cell growth under background radiation. Further network construction suggested that the enriched KEGG pathways affected this process by regulating cell proliferation-related genes including SMAD, SMAD7, CDH1, EGR1, and BMP2. Conclusions: Below-background radiation can lead to transcriptional changes in FD-LSC-1 cells cultured in the deep underground. The inhibitory growth effect is associated with multiple biological processes as well as canonical pathways of proliferation.

Whole Transcriptome Analysis Revealed a Stress Response to Deep Underground Environment Conditions in Chinese Hamster V79 Lung Fibroblast Cells.

Background: Prior studies have shown that the proliferation of V79 lung fibroblast cells could be inhibited by low background radiation (LBR) in deep underground laboratory (DUGL). In the current study, we revealed further molecular changes by performing whole transcriptome analysis on the expression profiles of long non-coding RNA (lncRNA), messenger RNA (mRNA), circular RNA (circRNA) and microRNA (miRNA) in V79 cells cultured for two days in a DUGL. Methods: Whole transcriptome analysis including lncRNA, mRNAs, circ RNA and miRNA was performed in V79 cells cultured for two days in DUGL and above ground laboratory (AGL), respectively. The differentially expressed (DE) lncRNA, mRNA, circRNA, and miRNA in V79 cells were identified by the comparison between DUGL and AGL groups. Quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to verify the selected RNA sequencings. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed for the DE mRNAs which enabled to predict target genes of lncRNA and host genes of circRNA. Results: With |log2(Fold-change)| ≥ 1.0 and p < 0.05, a total of 1257 mRNAs (353 mRNAs up-regulated, 904 mRNAs down-regulated), 866 lncRNAs (145 lncRNAs up-regulated, 721 lncRNAs down-regulated), and 474 circRNAs (247 circRNAs up-regulated, 227 circRNAs down-regulated) were significantly altered between the two groups. There was no significant difference in miRNA between the two groups. The altered RNA profiles were mainly discovered in lncRNAs, mRNAs and circRNAs. DE RNAs were involved in many pathways including ECM-RI, PI3K-Akt signaling, RNA transport and the cell cycle under the LBR stress of the deep underground environment. Conclusion: Taken together, these results suggest that the LBR in the DUGL could induce transcriptional repression, thus reducing metabolic process and reprogramming the overall gene expression profile in V79 cells.

Experimental and molecular dynamics study into the surfactant effect upon coal wettability.

In order to improve the wettability and permeability of coal seams, the water injection efficiency of coal seams has to be boosted, the amount of dust generation has to be reduced, and coal and gas outburst must be prevented, and a surfactant is used to modulate the coal surface wettability. In this work, taking coal samples from Pingdingshan mine in Henan as the research object, their surface chemistry was initially scrutinized and then coal surface engineering via surfactants was inspected by a contact angle test. The coal wettability was ameliorated with surfactants, particularly using the 1 wt% non-ionic surfactant Triton X-100, which elicited a 47% lower contact angle than the raw coal. The surface free energy of the coal sample modified by 1.0 wt% Triton X-100 was increased from 44.51 mN m-1 to 49.52 mN m-1. The microstructural characteristics of coal samples allowed leveraging the Wiser model to construct three kinds of surfactant-coal adsorption models to dissect the adsorption configuration of the system. The results indicate that the addition of surfactants increases both the interaction of water with the coal and the diffusion coefficient of water molecules, resulting in the coal surface transformation from hydrophobicity to hydrophilicity. Our current work can provide salutary guidance and reference for coal water injection and dust suppression.

Proteomic Characterization of Proliferation Inhibition of Well-Differentiated Laryngeal Squamous Cell Carcinoma Cells Under Below-Background Radiation in a Deep Underground Environment.

Background: There has been a considerable concern about cancer induction in response to radiation exposure. However, only a limited number of studies have focused on the biological effects of below-background radiation (BBR) in deep underground environments. To improve our understanding of the effects of BBR on cancer, we studied its biological impact on well-differentiated laryngeal squamous cell carcinoma cells (FD-LSC-1) in a deep underground laboratory (DUGL). Methods: The growth curve, morphological, and quantitative proteomic experiments were performed on FD-LSC-1 cells cultured in the DUGL and above-ground laboratory (AGL). Results: The proliferation of FD-LSC-1 cells from the DUGL group was delayed compared to that of cells from the AGL group. Transmission electron microscopy scans of the cells from the DUGL group indicated the presence of hypertrophic endoplasmic reticulum (ER) and a higher number of ER. At a cutoff of absolute fold change ≥ 1.2 and p < 0.05, 807 differentially abundant proteins (DAPs; 536 upregulated proteins and 271 downregulated proteins in the cells cultured in the DUGL) were detected. KEGG pathway analysis of these DAPs revealed that seven pathways were enriched. These included ribosome (p < 0.0001), spliceosome (p = 0.0001), oxidative phosphorylation (p = 0.0001), protein export (p = 0.0001), thermogenesis (p = 0.0003), protein processing in the endoplasmic reticulum (p = 0.0108), and non-alcoholic fatty liver disease (p = 0.0421). Conclusion: The BBR environment inhibited the proliferation of FD-LSC-1 cells. Additionally, it induced changes in protein expression associated with the ribosome, gene spliceosome, RNA transport, and energy metabolism among others. The changes in protein expression might form the molecular basis for proliferation inhibition and enhanced survivability of cells adapting to BBR exposure in a deep underground environment. RPL26, RPS27, ZMAT2, PRPF40A, SNRPD2, SLU7, SRSF5, SRSF3, SNRPF, WFS1, STT3B, CANX, ERP29, HSPA5, COX6B1, UQCRH, and ATP6V1G1 were the core proteins associated with the BBR stress response in cells.

Proteomics provides insights into the inhibition of Chinese hamster V79 cell proliferation in the deep underground environment.

As resources in the shallow depths of the earth exhausted, people will spend extended periods of time in the deep underground space. However, little is known about the deep underground environment affecting the health of organisms. Hence, we established both deep underground laboratory (DUGL) and above ground laboratory (AGL) to investigate the effect of environmental factors on organisms. Six environmental parameters were monitored in the DUGL and AGL. Growth curves were recorded and tandem mass tag (TMT) proteomics analysis were performed to explore the proliferative ability and differentially abundant proteins (DAPs) in V79 cells (a cell line widely used in biological study in DUGLs) cultured in the DUGL and AGL. Parallel Reaction Monitoring was conducted to verify the TMT results. γ ray dose rate showed the most detectable difference between the two laboratories, whereby γ ray dose rate was significantly lower in the DUGL compared to the AGL. V79 cell proliferation was slower in the DUGL. Quantitative proteomics detected 980 DAPs (absolute fold change ≥ 1.2, p < 0.05) between V79 cells cultured in the DUGL and AGL. Of these, 576 proteins were up-regulated and 404 proteins were down-regulated in V79 cells cultured in the DUGL. KEGG pathway analysis revealed that seven pathways (e.g. ribosome, RNA transport and oxidative phosphorylation) were significantly enriched. These data suggest that proliferation of V79 cells was inhibited in the DUGL, likely because cells were exposed to reduced background radiation. The apparent changes in the proteome profile may have induced cellular changes that delayed proliferation but enhanced survival, rendering V79 cells adaptable to the changing environment.

Physical symptoms and mental health status in deep underground miners: A cross-sectional study.

The aim of the present study was to reveal the physical symptom changes and their correlations with mental health status in deep underground miners.A total of 286 deep underground miners completed a cross-sectional questionnaire study at China Pingmei Shenma mine complex. The questionnaire included sociodemographics, self-reported physical symptoms, underground adverse environmental factors, and the Symptom Checklist-90-Revised (SCL-90-R). Five environmental parameters of 1 deep mine were also measured.Data from 266 valid questionnaires were analyzed. The 3 most frequent complaints about underground adverse conditions were moisture [62.03% (165/266)], dim light [45.86% (122/266)], and high temperature [42.11% (112/266)]. Fatigue [40.22% (107/266)], hearing loss [34.96% (93/266)], and tinnitus [31.58% (84/266)] were reported to be the three most common physical symptoms. Insomnia was reported in 204 participants (76.69%) mainly due to the difficulty of falling asleep [42.35% (84/204)] and dreams [39.70% (81/204)]. Mean scores of SCL-90-R subscales including somatization, anxiety, phobic anxiety, psychoticism, and paranoid ideation were elevated compared to Chinese norms, while there was diminished interpersonal sensitivity. Univariate analyses indicated that the 3 most common physical symptoms were associated with poorer SCL-90-R scores. With increasing depth below ground, air pressure, relative humidity, CO2 concentration and temperature rose, while total gamma radiation dose-rate decreased.The physical and mental health status of deep underground miners was poorer than the general Chinese male population. Some adverse environmental factors were identified that may have influenced health status. Measures are suggested to improve the deep underground working environment.

Subjective perceptions and psychological distress associated with the deep underground: A cross-sectional study in a deep gold mine in China.

This study reports the subjective perceptions and mental state of employees working in the Erdaogou Mine, affiliated with Jiapigou Minerals Limited Corporation of China National Gold Group Corporation (CJEM); these employees are pioneers working at the deepest point below ground in China. The data represent a valuable baseline from which to assess the effects of the environmental factors in the deep-underground on human physiology, psychology, and pathology.The air pressure, relative humidity, temperature, total γ radiation dose-rate, and oxygen concentration in the CJEM in the aisles in goafs at 4 depths below ground were measured. Study subjects were administered a study-specific questionnaire that included items that targeted factors with potential to affect respondents' health and wellbeing and included the symptom checklist-90-revised (SCL-90-R).Air pressure, relative humidity, and temperature rose, total γ radiation dose-rate decreased, and there was no change in oxygen concentration with increasing depth below ground. Most (97.2%) respondents had a negative impression of the ambient conditions in the deep-underground space. The most commonly perceived adverse factors included moisture (74.9%), heat (33.5%), and poor ventilation (32.4%). 93.29% of respondents associated ≥1 self-reported negative physical symptom with working in the deep-underground space; the most frequent symptoms were being easily tired (48.7%), tinnitus (47.5%), and hearing loss (44.1%). Higher SCL-90-R scores were associated with the perception of >1 adverse factor in the deep-underground, spending >8 hours continuously in the deep-underground space, or working at a depth > 1000 m below ground. >1 perceived adverse factor in the deep-underground and continuously spending >8 hours in the deep-underground space were significant predictors of high SCL-90-R scores.Adverse factors, including high temperature, humidity, and dim light, may have negative impacts on the physical and psychological health of people who spend long periods of time living and/or working in the deep-underground space.

History, advancements, and perspective of biological research in deep-underground laboratories: A brief review.

The world is entering a new era of exploring and exploiting the deep-underground space. With humans poised to reach historical depths in the use of the deep Earth, it is essential to understand the effect of the deep-underground environment on the health of humans and other living organisms. This article outlines the history and development of biological research conducted in deep-underground laboratories and provides insight into future areas of investigation. Many deep-underground laboratories have investigated the effects of reduced cosmic ray muons flux, searching for rare events such as proton decay, dark matter particles, or neutrino interactions, but few have focused on the influence of the environmental factors in the deep-underground on living organisms. Some studies revealed that prokaryote and eukaryote cells maintained in low levels of background radiation exhibited an stress response, which manifested as changes in cell growth, enzyme activity, and sensitivity to factors that cause genetic damage; however, the underlying mechanisms are unclear. There remains an urgent need to understand the detrimental and beneficial biological effects of low background radiation and other factors in the deep-underground on humans and other organisms. Consequently, a multidisciplinary approach to medical research in the deep-underground has been proposed, creating a new discipline, deep-underground medicine, and representing a historical milestone for exploring the deep Earth and in medical research.

[The Research Advancement and Conception of the Deep-underground Medicine].

The 21th century is the century of exploring and utilizing the underground space. In the future, more and more people will spend more and more time living or/and working in the underground space. However,we know little about the effect on the health of human caused by the underground environment. Herein,we systematically put forward the strategic conception of the deep-underground medicine,in order to reveal relative effects and mechanism of the potential factors in the deep underground space on human's physiological and psychological healthy,and to work out the corresponding countermeasures. The original deep-underground medicine includes the following items. ①To model different depth of underground environment according to various parameters (such as temperature,radiation,air pressure, rock,microorganism), and to explore their quantitative character and effects on human health and mechanism. ② To study the psychological change, maintenance of homeostasis and biothythm of organism in the deep underground space. ③ To learn the association between psychological healthy of human and the depth, structure, physical environment and working time of underground space. ④ To investigate the effect of different terrane and lithology on healthy of human and to deliberate their contribution on organism growth. ⑤ To research the character and their mechanism of growth,metabolism,exchange of energy,response of growth, aging and adaptation of cells living in deep underground space. ⑥ To explore the physiological feature,growth of microbiome and it's interaction with host in the deep underground space. ⑦ To develop deep-underground simulation space, the biologically medical technology and equipments. As a research basis,a deep-underground medical lab under a rock thickness of about 1 470 m has been built,which aims to operate the research of the effect on living organism caused by different depth of underground environment.

Derivation and application of an analytical rock displacement solution on rectangular cavern wall using the inverse mapping method.

Rectangular caverns are increasingly used in underground engineering projects, the failure mechanism of rectangular cavern wall rock is significantly different as a result of the cross-sectional shape and variations in wall stress distributions. However, the conventional computational method always results in a long-winded computational process and multiple displacement solutions of internal rectangular wall rock. This paper uses a Laurent series complex method to obtain a mapping function expression based on complex variable function theory and conformal transformation. This method is combined with the Schwarz-Christoffel method to calculate the mapping function coefficient and to determine the rectangular cavern wall rock deformation. With regard to the inverse mapping concept, the mapping relation between the polar coordinate system within plane ς and a corresponding unique plane coordinate point inside the cavern wall rock is discussed. The disadvantage of multiple solutions when mapping from the plane to the polar coordinate system is addressed. This theoretical formula is used to calculate wall rock boundary deformation and displacement field nephograms inside the wall rock for a given cavern height and width. A comparison with ANSYS numerical software results suggests that the theoretical solution and numerical solution exhibit identical trends, thereby demonstrating the method's validity. This method greatly improves the computing accuracy and reduces the difficulty in solving for cavern boundary and internal wall rock displacements. The proposed method provides a theoretical guide for controlling cavern wall rock deformation failure.