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Coal seam mining causes fracture and movement of overlying strata in goaf, and endangers the safety of surface structures and underground pipelines. Based on the engineering geological conditions of 22,122 working face in Cuncaota No.2 Coal Mine of China Shenhua Shendong Coal Group Co., Ltd. a similar material model test of mining overburden rock was carried out. The subsidence of overburden rock was obtained through the full-section strain data of distributed optical fiber technology, and the characteristics of mining surface subsidence were studied. The Weibull model was used to adjust the mathematical form of the first half of the surface subsidence curve via the MMF function. On this basis, the prediction model of coal seam mining surface subsidence was established, and the parameters of the prediction model of surface subsidence were determined. The test results show that with the advancement of coal seam mining, the fit goodness of the surface subsidence prediction curve based on the MMF optimization model reaches 0.987. Compared with the measured values, the relative error of the surface subsidence prediction model is reduced to less than 10%. The model displays good prediction accuracy. The time required for settlement stability in the prediction model is positively correlated with parameter a and negatively correlated with parameter b. The research results can be further extended to the prediction of overburden "three zones" subsidence, and provide a scientific basis for the evaluation of surface subsidence compression potential in coal mine goaf., (© 2024. The Author(s).)

To explore the molecular pathogenesis of pulmonary arterial hypertension (PAH) and identify potential therapeutic targets, we performed transcriptome sequencing of lung tissue from mice with hypoxia-induced pulmonary hypertension. Our Gene Ontology analysis revealed that "extracellular matrix organization" ranked high in the biological process category, and matrix metallopeptidases (MMPs) and other proteases also played important roles in it. Moreover, compared with those in the normoxia group, we confirmed that MMPs expression was upregulated in the hypoxia group, while the hub gene Timp1 was downregulated. Crocin, a natural MMP inhibitor, was found to reduce inflammation, decrease MMPs levels, increase Timp1 expression levels, and attenuate hypoxia-induced pulmonary hypertension in mice. In addition, analysis of the cell distribution of MMPs and Timp1 in the human lung cell atlas using single-cell RNAseq datasets revealed that MMPs and Timp1 are mainly expressed in a population of fibroblasts. Moreover, in vitro experiments revealed that crocin significantly inhibited myofibroblast proliferation, migration, and extracellular matrix deposition. Furthermore, we demonstrated that crocin inhibited TGF-β1-induced fibroblast activation and regulated the pulmonary arterial fibroblast MMP2/TIMP1 balance by inhibiting the TGF-β1/Smad3 signaling pathway. In summary, our results indicate that crocin attenuates hypoxia-induced pulmonary hypertension in mice by inhibiting TGF-β1-induced myofibroblast activation., (© 2024. The Author(s).)

In order to meet the personalized needs of Chinese intelligent vehicles and improve the satisfaction and acceptance of human-computer interaction and collaboration in domestic intelligent vehicles. In this paper, we design an adaptive longitudinal following model that integrates the perceptual perturbation process and driver characteristics for simulating driver following behavior and studying the variability of driver following behavior. Firstly, for the independence and randomness of driver perception process, a set of random variables conforming to Wiener process is introduced to simulate the perception process of speed and following distance of the vehicle in front; secondly, for the characteristic differences of different drivers' following behavior, a driver characteristic parameter identification algorithm is designed to identify the expected collision time distance and following distance parameters of different drivers, and the identified parameters will be used for Again, a sliding mode control system based on fuzzy switching gain adjustment is designed to simulate the driver following control system. The results show that the designed following model recognizes the driver's characteristics well and can better simulate the driver's following behavior, and the following index is relatively improved by 80%., (© 2022. The Author(s).)

Twisted and coiled actuators (TCAs), fabricated by twisting cheap nylon sewing threads, have attracted a great deal of attention for their use as artificial muscles or soft actuators. Since the dynamic behavior of a thermally-operated TCA is governed by its thermal properties, graphene and silver nanoflowers (AgNFs) were spray-coated onto the surface of an actuator to achieve enhanced heat transfer. Addition of AgNFs improves interfacial thermal contacts between graphene flakes, while pristine graphene flakes have extremely high in-plane thermal conductivity. Thus, the synergistic effect of graphene and AgNFs reduced the total cycle time of the TCA by up to 38%. Furthermore, when a pulsed current with a 40% duty cycle was applied to the TCA, the graphene/AgNF-coated TCA exhibited a threefold larger peak-to-peak amplitude of the displacement oscillation of the actuator, as compared to that of the non-coated TCA, which demonstrates that the combination of graphene and AgNFs effectively reduced a cooling time of the TCA. This work shows great potential for a simple coating of graphene and AgNFs to produce high-performance thermally-operated soft actuators.

S100A12 belongs to the S100 family and acts as a vital regulator in different types of tumors. However, the function of S100A12 in thyroid carcinoma has not yet been investigated. In this study, we analyzed the expression of S100A12 in human papillary thyroid cancer (PTC) samples and two PTC cell lines. In addition, we explored the effects of S100A12 on PTC cell progression in vitro and in vivo. Our results showed that S100A12 was significantly upregulated in PTC specimens. Moreover, silencing S100A12 markedly inhibited PTC cell proliferation, migration, invasion and cell cycle progression. In addition, knockdown of S100A12 significantly reduced the expression of CyclinD1, CDK4 and p-ERK in PTC cells. An in vivo study also showed that silencing S100A12 dramatically suppressed tumor cell growth and decreased Ki67 expression in a xenograft mouse model. This study provides novel evidence that S100A12 serves as an oncogene in PTC. Knockdown of S100A12 suppressed PTC cell proliferation, migration, and invasion and induced G0/G1 phase arrest via the inhibition of the ERK signaling pathway. Therefore, S100A12 may be a potent therapeutic target for PTC.

Thoracic aortic dissection (TAAD) is one of the most common types of aortic diseases. Although surgery remains the main method of treatment, the high rate of postoperative gastrointestinal complications significantly influences the effects of surgery and the recovery process. Moreover, the mechanisms underlying this disease remain unclear. To address these problems, we examined changes in the gut microbiota in 40 thoracic aortic dissection patients with abdominal complications after surgery. Levels of white blood cells (WBC), neutrophile granulocytes (NE), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were higher in all patients after surgery. Levels of inflammatory cytokines, including interleukin (IL)-2, IL-6, IL-8, and IL-10, were also higher after surgery. A metagenome analysis revealed that levels of Oscillibacter, Anaerotruncus, Alistipes, and Clostridium difficile were higher after the operation. The abundance of functional genes, such as the spermidine/putrescine transport system permease protein, the flagellar motor switch protein, and branched-chain amino acid transport system proteins, was also higher post-surgery. These changes likely contribute to diarrhea, bloating, gastrointestinal bleeding, and other abdominal complications after surgery, and our research opens up new treatment possibilities for patients suffering from abdominal complications after surgical treatment.

Thoracic aortic dissection (TAD) is a catastrophic disease with high mortality and morbidity, characterized by fragmentation of elastin and loss of smooth muscle cells. However, the underlying pathological mechanisms of this disease remain elusive because there are no appropriate animal models, limiting discovery of effective therapeutic strategies. We treated mice on C57BL/6 and FVB genetic backgrounds with β-aminopropionitrile monofumarate (BAPN), an irreversible inhibitor of lysyl oxidase, for 4 wk, followed by angiotensin II (Ang II) infusion for 24 h. We found that the BAPN plus Ang II treatment induced formation of aortic dissections in 100% of mice on both genetic backgrounds. BAPN without Ang II caused dissections in few FVB mice, but caused 87% of C57BL/6 mice to develop TAD, with 37% dying from rupture of the aortic dissection. Moreover, a lower dose of BAPN induced TAD formation and rupture earlier with fewer effects on body weight. Therefore, we have generated a reliable and convenient TAD model in C57BL/6 mice for studying the pathological process and exploring therapeutic targets of TAD.

Genetic etiology in majority of patients with sporadic thoracic aortic aneurysm and dissections (STAAD) remains unknown. Recent GWAS study suggested common variant(s) in FBN1 is associated with STAAD. The present study aims to test this hypothesis and to identify mutation spectrum by targeted exome sequencing of the FBN1 gene in 146 unrelated patients with STAAD. Totally, 15.75% of FBN1 variants in STAAD were identified, including 5 disruptive and 18 missense mutations. Most of the variants were novel. Genotype-phenotype correlation analysis suggested that the maximum aortic diameter in the disruptive mutation group was significantly larger than that in the non-Cys missense mutation group. Interestingly, the variant Ala27Thr at -1 position, which is predicted to change the cleavage site of the signal peptidase of fibrillin-1, was detected in two unrelated patients. Furthermore, genotyping analysis of this variant detected 10 heterozygous Ala27Thr from additional 666 unrelated patients (1.50%), versus 7 from 1500 controls (0.47%), indicating a significant association of this variant with STAAD. Collectively, the identification of the variant Ala27Thr may represent a relatively common genetic predisposition and a novel pathogenetic mechanism for STAAD. Also, expansion of the mutation spectrum in FBN1 will be helpful in genetic counselling for Chinese patients with STAAD.

Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death. Mutations in the MYBPC3 gene represent the cause of HCM in ~35% of patients with HCM. However, genetic testing in clinic setting has been limited due to the cost and relatively time-consuming by Sanger sequencing. Here, we developed a HCM Molecular Diagnostic Kit enabling ultra-low-cost targeted gene resequencing in a large cohort and investigated the mutation spectrum of MYBPC3. In a cohort of 114 patients with HCM, a total of 20 different mutations (8 novel and 12 known mutations) of MYBPC3 were identified from 25 patients (21.9%). We demonstrated that the power of targeted resequencing in a cohort of HCM patients, and found that MYBPC3 is a common HCM-causing gene in Chinese patients. Phenotype-genotype analyses showed that the patients with double mutations (n = 2) or premature termination codon mutations (n = 12) showed more severe manifestations, compared with patients with missense mutations (n = 11). Particularly, we identified a recurrent truncation mutation (p.Y842X) in four unrelated cases (4/25, 16%), who showed severe phenotypes, and suggest that the p.Y842X is a frequent mutation in Chinese HCM patients with severe phenotypes.

The tumor suppressor p53 is an important regulator of intracellular reactive oxygen species (ROS) levels, although downstream mediators of p53 remain to be elucidated. Here, we show that p53 and its downstream targets, p53-inducible ribonucleotide reductase (p53R2) and p53-inducible gene 3 (PIG3), physically and functionally interact with catalase for efficient regulation of intracellular ROS, depending on stress intensity. Under physiological conditions, the antioxidant functions of p53 are mediated by p53R2, which maintains increased catalase activity and thereby protects against endogenous ROS. After genotoxic stress, high levels of p53 and PIG3 cooperate to inhibit catalase activity, leading to a shift in the oxidant/antioxidant balance toward an oxidative status, which could augment apoptotic cell death. These results highlight the essential role of catalase in p53-mediated ROS regulation and suggest that the p53/p53R2-catalase and p53/PIG3-catalase pathways are critically involved in intracellular ROS regulation under physiological conditions and during the response to DNA damage, respectively.

The p53-dependent RR small subunit (p53R2) protein, a newly identified member of the ribonucleotide reductase family, plays a key role in the p53-dependent cellular response to DNA. Several recent studies have suggested that p53R2 also plays an important role in suppressing the invasive potential of human cancer cells. However, the cellular mechanism that regulates invasiveness remains largely unknown. In this study, we show that p53R2 interacts with MEK2 (extracellular signal-regulated kinase (ERK) kinase 2-mitogen-activated protein kinase (MAPK) kinase 2), the molecule immediately upstream of ERK in the Ras-Raf-MAPK signaling cascade. In co-immunoprecipitation and immunofluorescence analyses, we found that p53R2 and MEK2 interact physically in cultured mammalian cells, and that the p53R2 segment comprising amino acids 161-206 is critical for this interaction. Moreover, serum-induced phosphorylation of MEK1/2 and ERK1/2 was greatly augmented in human cancer cells expressing small-interfering RNA against p53R2. On the other hand, phosphorylation of MEK1/2 and ERK1/2 in human cancer cells was markedly attenuated by overexpression of p53R2. Furthermore, MEK2 was required for p53R2 knockdown-induced enhancement of the invasive ability and anchorage-independent growth of human lung cancer H1299 cells. Taken together, these findings show that p53R2 negatively modulates serum-induced MEK-ERK activity and inhibits the MEK-ERK-mediated malignancy potential of human cancer cells.

Currently, the pathogenesis of chronic GVHD is unclear. To elucidate the molecular characteristics underlying chronic GVHD, we analyzed the gene expression profiles of 21 mononuclear cell samples from allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Self organizing map (SOM) clustering showed that the entire expression profiles of chronic GVHD samples were clearly different from those of the non-GVHD samples, and significance analysis of microarray (SAM) demonstrated that 120 genes, including PTDSS1, VAV1 and CD3D, were up-regulated, and 5 genes, including calnexin, were down-regulated in GVHD patients. Gene ontology annotation revealed that these genes are related to the phosphorous metabolism and lipid biosynthesis. Quantitative real time polymerase chain reaction (qRT-PCR) experiments validated the up-regulation of PTDSS1, VAV1 and CD3D in separate samples. Pathway-wise global test revealed that differential gene expression in cell cycle and T cell immune-associated pathways were significant between GVHD patients and non-GVHD patients. Seventeen classifier genes selected using a PAM (prediction analysis of microarray) algorithm showed favorable performance (prediction accuracy=0.85) for identifying patients with chronic GVHD. In conclusion, we identified differentially expressed genes and pathways in chronic GVHD patients using microarray analysis, and we also selected diagnostic genes predicting chronic GVHD status.

Although asbestos is carcinogenic to humans, the mechanism(s) by which it induces cancer is unknown. Using tumor cell lines generated previously by asbestos treatment of immortalized human bronchial epithelial (BEP2D) cells, we examined alterations in p16 and p21(Cip1) genes together with their protein levels. Results were compared with untreated BEP2D cells, normal human bronchial epithelial cells (NHBE), as well as non-tumorigenic fusion cell lines generated by fusing tumor cells with BEP2D cells. No deletion in the p16 gene was found in any of the tumor cell lines examined. Although p16 protein was expressed at a similar level in tumor and BEP2D cells, there was a fourfold decrease in its expression among NHBE cells. In contrast, both the protein and mRNA expression levels of p21(Cip1) were decreased by about threefold in tumor cell lines when compared with either BEP2D or NHBE cells, which had a similar expression level. Expression of p21(Cip1) mRNA was restored to the control level in all the fusion cell lines examined. The results suggested that down regulation of p21(Cip1) expression is linked to the tumorigenic conversion of BEP2D cells by asbestos.

Chromosome end-to-end associations seen at metaphase involve telomeres and are commonly observed in cells derived from individuals with ataxia telangiectasia and most types of human tumors. The associations may arise because of short telomeres and/or alterations of chromatin structure. There is a growing consensus that telomere length is stabilized by the activity of telomerase in immortal cells; however, it is not clear why some immortal cells display chromosome end-to-end associations. In the present study we evaluated chromosome end-to-end associations, telomere length and telomerase activity with the tumorigenic status of human bronchial epithelial cells immortalized with human papillomavirus. Oncogenic transformation was initiated using radon simulated alpha-particles and cells evaluated as primary, secondary and metastatic transformants. The fewest chromosome end associations and lowest telomerase activity were observed in the parental immortalized cells. However, increased levels of telomerase activity were detected in alpha-particle survivors while robust telomerase activity was seen in the tumorigenic cell lines. The tumorigenic cells that were telomerase positive and had the highest frequency of cells with chromosome end-to-end associations were also metastatic. No correlation was found between telomere length and the different stages of carcinogenicity.