A facile nanozyme-based colorimetric method to realize the quantitative and specific detection of casein phosphopeptides in food samples.

As a popular nutritional enhancer, casein phosphopeptides (CPPs) have attracted growing attention in food industry. However, conventional methods for CPPs detection are usually less precise or requires expensive instruments. Herein, a nanozyme-based colorimetric method was developed to achieve the quantitative detection of CPPs in food samples. This method is based on a facilely fabricated peroxidase-like nanozyme (Fe@UiO-66), which combines the specific binding of CPPs, as well as the nanozyme-catalyzed colorimetric sensing that can be easily detected by spectrometer. The method displayed good quantitative ability toward CPPs with the linear range of 2-30 µg/mL, the low limit of detection of 0.267 µg/mL and limit of quantification of 1.335 µg/mL. We highlighted the specificity, anti-interference and practicability of this method, by investigating the performances toward food samples. Besides, a smartphone-based colorimetric sensing platform was also established, which is conducive to the portable detection. The developed nanozyme-based colorimetric sensing method provides a promising strategy for CPPs detection in food samples.

Hybrid Water-Harvesting Channels Delivering Wide-Range and Supersensitive Passive Fluorescence Humidity Sensors.

The development of optical humidity detection has been of considerable interest in highly integrated wearable electronics and packaged equipment. However, improving their capacities for color recognition at ultralow humidity and response-recovery rate remains a significant challenge. Herein, we propose a type of hybrid water-harvesting channel to construct brand-new passive fluorescence humidity sensors (PFHSs). Specifically, the hybrid water-harvesting channels involve porous metal-organic frameworks and a hydrophilic poly(acrylic acid) network that can capture water vapors from the ambient environment even at ultralow humidity, into which polar-responsive aggregation-induced emission molecules are doped to impart humidity-sensitive luminescence colors. As a result, the PFHSs exhibit clearly defined fluorescence signals within 0-98% RH coupling with desirable performances such as a fast response rate, precise quantitative feedback, and durable reversibility. Given the flexible processability of this system, we further upgrade the porous structure via electrostatic spinning to furnish a kind of Nano-PFHSs, demonstrating an impressive response time (<100 ms). Finally, we validate the promising applications of these sensors in electronic humidity monitoring and successfully fabricate a portable and rapid humidity indicator card.

Immobilization-free and label-free electrochemical DNA biosensing based on target-stimulated release of redox reporter and its catalytic redox recycling.

Herein, we demonstrate a simple, homogenous and label-free electrochemical biosensing system for sensitive nucleic acid detection based on target-responsive porous materials and nuclease-triggered target recycling amplification. The Fe(CN)63- reporter was firstly sealed into the pores of Fe3O4 nanoparticles by probe DNA. Target DNA recognition triggered the controllable release of Fe(CN)63- for the redox reaction with the electron mediator of methylene blue enriched in the dodecanethiol assembled electrode and thereby generating electrochemical signal. The exonuclease III (Exo III)-assisted target recycling and the catalytic redox recycling between Fe(CN)63- and methylene blue contributed for the enhanced signal response toward target recognition. The low detection limit toward target was obtained as 478 fM and 1.6 pM, respectively, by square wave voltammetry and cyclic voltammetry methods. It also possessed a well-discrimination ability toward mismatched strands and high tolerance to complex sample matrix. The coupling of bio-gated porous nanoparticles, nuclease-assisted target amplification and catalytic redox recycling afforded the sensing system with well-controllable signal responses, sensitive and selective DNA detection, and good stability, reusability and reproducibility. It thus opens a new avenue toward the development of simple but sensitive electrochemical biosensing platform.

Biochar with enhanced performance prepared based on "graphite-structure regulation" conjecture designed to effectively control water pollution.

In this work, corn straw was used as raw material, Hummers method and activation were used to adjust the graphite structure in biochar, and preparing straw based biochar (H-BCS) with ultra-high specific surface area (3441.80 m2/g), highly total pore volume (1.9859 cm3/g), and further enhanced physicochemical properties. Compared with untreated straw biochar (BCS), the specific surface area and total pore volume of H-BCS were increased by 47.24 % and 55.85 %, respectively. H-BCS showed good removal ability in subsequent experiments by using chloramphenicol (CP), hexavalent chromium (Cr6+), and crystal violet (CV) as adsorption models. In addition, the adsorption capacities of H-BCS (CP: 1396.30 mg/g, Cr6+: 218.40 mg/g, and CV: 1246.24 mg/g) are not only higher than most adsorbents, even after undergoing 5 cycles of regeneration, its adsorption capacity remains above 80 %, indicating significant potential for practical applications. In addition, we also speculated and analyzed the conjecture about the "graphite-structure regulation" during the preparation process, and finally discussed the possible mechanism during the adsorption processes. We hope this work could provide a new strategy to solve the restriction of biochar performance by further exploring the regulation of graphite structure in carbon materials.

Circularly Polarized Room Temperature Phosphorescence through Twisting-induced Helical Structures from Polyvinyl Alcohol-based Fibers Containing Hydrogen-bonded Dyes.

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6%, and the improved tensile strength being 1.7 times than pure PVA fiber (172 ± 5.82 vs 100 ± 5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.

PIM1 alleviated liver oxidative stress and NAFLD by regulating the NRF2/HO-1/NQO1 pathway.

AIMS: Non-alcoholic fatty liver disease (NAFLD) has risen as a significant global public health issue, for which vertical sleeve gastrectomy (VSG) has become an effective treatment method. The study sought to elucidate the processes through which PIM1 mitigates the advancement of NAFLD. The Pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) functions as a serine/threonine kinase. Bioinformatics analysis revealed that reduced PIM1 expression in NAFLD. METHODS: To further prove the role of PIM1 in NAFLD, an in-depth in vivo experiment was performed, in which male C57BL/6 mice were randomly grouped to receive a normal or high-fat diet for 24 weeks. They were operated or delivered the loaded adeno-associated virus which the PIM1 was overexpressed (AAV-PIM1). In an in vitro experiment, AML12 cells were treated with palmitic acid to induce hepatic steatosis. KEY FINDINGS: The results revealed that the VSG surgery and virus delivery of mice alleviated oxidative stress, and apoptosis in vivo. For AML12 cells, the levels of oxidative stress, apoptosis, and lipid metabolism were reduced via PIM1 upregulation. Moreover, ML385 treatment resulted in the downregulation of the NRF2/HO-1/NQO1 signaling cascade, indicating that PIM1 mitigates NAFLD by targeting this pathway. SIGNIFICANCE: PIM1 alleviated mice liver oxidative stress and NAFLD induced by high-fat diet by regulating the NRF2/HO-1/NQO1 signaling Pathway.

Hepatitis B: Model Systems and Therapeutic Approaches.

Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus's life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.

B-cell targeted therapies in autoimmune encephalitis: mechanisms, clinical applications, and therapeutic potential.

Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.

A vascularized adipose organoid model using stromal vascular fraction cells from ruminant animals.

In vitro cell culture serves as an efficient system for studying animal cell behavior in a controlled setting. Here, we present a 3D culture model for forming ruminant adipose organoids using stromal vascular fraction cells. We describe steps for forming cell spheroids and growing them on a Matrigel-coated surface. We then detail procedures for inducing organoids to undergo angiogenesis and adipogenesis followed by capillary sprouting. This protocol can be utilized to study the interaction between blood vessels and adipocytes. For complete details on the use and execution of this protocol, please refer to Yu et al.1.

The role of endoplasmic reticulum stress-related genes in the diagnosis and subtyping of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Chronic activation of endoplasmic reticulum stress (ERS) in hepatocytes may promote the development of NAFLD, yet endoplasmic reticulum stress-related genes (ERSGs) have not been studied in NAFLD. Our aim is to study the relationship between ERSGs and the immune microenvironment of NAFLD patients and to construct predictive models. We screened 48 endoplasmic reticulum stress-related differentially expressed genes (ERSR-DEGs) using data from two GEO datasets and the GeneCards database. Enrichment analysis revealed that ERSR-DEGs are closely associated with immune-related pathways and functions. The immune infiltration profile of NAFLD was obtained by single sample gene set enrichment analysis (ssGSEA). There were significant differences in immune cell infiltration and immune function between NAFLD group and control group. Using 113 NAFLD samples, we explored two molecular clusters based on ERSR-DEGs. A five-gene SVM model was selected as the best machine learning model, and a nomogram based on five-gene SVM model showed good predictive efficiency. The mRNA expression levels of POR, PPP1R15A, FOS and FAS were significantly different between NAFLD mice and healthy mice. In conclusion, ERS is closely associated with the development of NAFLD. We established a promising and SVM-based predictive model to assess the risk of disease in patients with ERS subtypes and NAFLD.

Visual detection of H2O2 and glucose by HBcAb-HRP fluorescence-enhanced CdTe QDs/CDs ratiometric fluorescence sensing platform.

This study presents the development of a sensitive and simple enhanced ratiometric fluorescence sensing platform in the consist of CdTe quantum dots (QDs), carbon dots (CDs), and hepatitis B core antibody labeled with horseradish peroxidase (HBcAb-HRP) for the visual analysis of H2O2 and glucose. The sulfur atoms in HBcAb-HRP have a strong affinity for Cd(II), which effectively enhances the fluorescence intensity of the CdTe QDs due to the generation of more radiative centers at the CdTe/Cd-SR complex. In the presence of H2O2, the Cd-S bonds are oxidized to form disulfide products and results in linear fluorescence quenching, while CDs maintain stable. Becasue glucose can be converted into H2O2 with the aid of glucose oxidase, this sensing platform can also be used for analyzing glucose. The detection limits for H2O2 and glucose are 2.9 µmol L-1 with RSD of 2.6% and 1.6 µmol L-1 with RSD of 2.4% respectively. In addition, under UV lamp irradiation, the orange-yellow CdTe QDs gradually quench with increasing H2O2 and glucose, while the blue CDs remain unchanged. A color change from orange-yellow to blue enables a visual semi-quantitative determination of H2O2 in commercial contact lens solution and glucose in human serum without any pretreatment. Thus, this CdTe QDs/CDs ratiometric sensing platform has significant potential for the rapid analysis of H2O2 and glucose in actual application.

Distinct bile acid alterations in response to a single administration of PFOA and PFDA in mice.

Per- and polyfluoroalkyl substances (PFASs), a group of synthetic chemicals that were once widely used for industrial purposes and in consumer products, are widely found in the environment and in human blood due to their extraordinary resistance to degradation. Once inside the body, PFASs can activate nuclear receptors such as PPARα and CAR. The present study aimed to investigate the impact of perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) on liver structure and functions, as well as bile acid homeostasis in mice. A single administration of 0.1 mmole/kg of PFDA, not PFOA, elevated serum ALT and bilirubin levels and caused cholestasis in WT mice. PFDA increased total and various bile acid species in serum but decreased them in the liver. Furthermore, in mouse livers, PFDA, not PFOA, down-regulated mRNA expression of uptake transporters (Ntcp, Oatp1a1, 1a4, 1b2, and 2b1) but induced efflux transporters (Bcrp, Mdr2, and Mrp2-4). In addition, PFDA, not PFOA, decreased Cyp7a1, 7b1, 8b1, and 27a1 mRNA expression in mouse livers with concomitant hepatic accumulation of cholesterol. In contrast, in PPARα-null mice, PFDA did not increase serum ALT, bilirubin, or total bile acids, but produced prominent hepatosteatosis; and the observed PFDA-induced expression changes of transporters and Cyps in WT mice were largely attenuated or abolished. In CAR-null mice, the observed PFDA-induced bile acid alterations in WT mice were mostly sustained. These results indicate that, at the dose employed, PFDA has more negative effects than PFOA on liver function. PPARα appears to play a major role in mediating most of PFDA-induced effects, which were absent or attenuated in PPARα-null mice. Lack of PPARα, however, exacerbated hepatic steatosis. Our findings indicate separated roles of PPARα in mediating the adaptive responses to PFDA: protective against hepatosteatosis but exacerbating cholestasis.

Experimental study on the significance of pressure relief effect and crack extension law under uniaxial compression of rock-like materials containing drill holes.

The drilling pressure relief technology is an effective way to reduce the accumulation of elastic energy in the tunnel envelope, which can reduce the risk of regional ground pressure occurrence. However, there is a lack of theoretical guidance on which drilling parameter has the greatest degree of influence on the effectiveness of pressure relief. The uniaxial compression tests were conducted to study the relationships between drilling parameters (the diameter, depth, and spacing) and the mechanical properties and deformation modulus of specimens. The results show that: (1) The drilling diameter (DDR) and drilling depth (DDH) of single-hole specimens negatively correlate with the peak-failure strength and deformation modulus, while the drilling spacing (DS) of double-hole specimens positively correlates with the peak-failure strength and deformation modulus. It shows that the borehole diameter has a more significant effect on the decompression effect. (2) With the help of the Grey Relational Analysis, the factors affecting the peak-failure strength and deformation modulus of the drilled specimens were ranked in significance. From the largest to the smallest, they are DDR, followed by DDH and DS. (3) The role of the pressure relief mechanism is to transfer the high stress in the shallow part of the roadway to the deep part, reduce the peak strength of destruction and deformation modulus of the peripheral rock in the drilled section, so that the characteristics of the mechanical behavior of the rock are significantly weakened, and the range of the area of the drilled hole decompression is enlarged. During the loading of the borehole, the borehole stress field dominates in the early stage, and cracking starts near the borehole along the direction perpendicular to the direction of maximum principal stress (horizontal direction). In the later stage, the maximum principal stress field dominates and vertical cracks with large widths appear. During crack expansion, the plastic energy dissipation effect is enhanced and the deep impact conduction path is weakened, thus protecting the roadway. This study determined the significance of the pressure relief effect of different drilling parameters, which can guide reasonable modifications of drilling parameters in the field.

Co-immobilized multi-enzyme biocatalytic system on reversible and soluble carrier for saccharification of corn straw cellulose.

Herein, three enzymes (cellulase, ß-glucosidase, and pectinase) with synergistic effects were co-immobilized on the Eudragit L-100, and the recovery of co-immobilized enzymes from solid substrates were achieved through the reversible and soluble property of the carrier. The optimization of enzyme ratio overcomed the problem of inappropriate enzyme activity ratio caused by different immobilization efficiencies among enzymes during the preparation process of co-immobilized enzymes. The co-immobilized enzymes were utilized to catalytically hydrolyze cellulose from corn straw into glucose, achieving a cellulose conversion rate of 74.45% under conditions optimized for their enzymatic characteristics and hydrolytic reaction conditions. As a result of the reversibility and solubility of the carrier, the co-immobilized enzymes were recovered from the solid substrate after five cycles, retaining 54.67% of the enzyme activity. The aim of this study is to investigate the potential of co-immobilizing multiple enzymes onto the Eudragit L-100 carrier for the synergistic degradation of straw cellulose.

Identification and validation of cuproptosis-related molecular clusters in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease worldwide. Cuproptosis has recently been reported as a form of cell death that appears to drive the progression of a variety of diseases. This study aimed to explore cuproptosis-related molecular clusters and construct a prediction model. The gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. The associations between molecular clusters of cuproptosis-related genes and immune cell infiltration were investigated using 50 NAFLD samples. Furthermore, cluster-specific differentially expressed genes were identified by the WGCNA algorithm. External datasets were used to verify and screen feature genes, and nomograms, calibration curves and decision curve analysis (DCA) were performed to verify the performance of the prediction model. Finally, a NAFLD-diet mouse model was constructed to further verify the predictive analysis, thus providing new insights into the prediction of NAFLD clusters and risks. The role of cuproptosis in the development of non-alcoholic fatty liver disease and immune cell infiltration was explored. Non-alcoholic fatty liver disease was divided into two cuproptosis-related molecular clusters by unsupervised clustering. Three characteristic genes (ENO3, SLC16A1 and LEPR) were selected by machine learning and external data set validation. In addition, the accuracy of the nomogram, calibration curve and decision curve analysis in predicting NAFLD clusters was also verified. Further animal and cell experiments confirmed the difference in their expression in the NAFLD mouse model and Mouse hepatocyte cell line. The present study explored the relationship between non-alcoholic fatty liver disease and cuproptosis, providing new ideas and targets for individual treatment of the disease.

Arctigenin promotes mucosal healing in ulcerative colitis through facilitating focal adhesion assembly and colonic epithelial cell migration via targeting focal adhesion kinase.

Colonic mucosal defect constitutes the major reason of recurrence and deterioration of ulcerative colitis (UC), and mucosal healing has become the therapeutic endpoint of UC. Unfortunately, specific promoter of mucosal healing is still absent. Our previous researches demonstrated that arctigenin could alleviate colitis symptoms in mice, but whether it has a positive impact on colonic mucosal healing remains unclear. This study explores whether and how arctigenin promotes mucosal healing. Orally administered arctigenin was shown to alleviate colitis in mice primarily by enhancing mucosal healing. In vitro, arctigenin was shown to promote the wound healing by accelerating colonic epithelial cell migration but not proliferation. Acceleration of the focal adhesion turnover, especially assembly, is crucial for arctigenin promoting the cell migration. Arctigenin was able to activate focal adhesion kinase (FAK) in colonic epithelial cells through directly binding with Tyr251 site of FAK, as evidenced by surface plasmon resonance assay and site-directed mutagenesis experiment. In the colonic epithelial cells of UC patients and colitis mice, FAK activation was significantly down-regulated compared with the controls. Arctigenin promoted colonic epithelial cell migration and mucosal healing in dextran sulphate sodium (DSS)-induced colitis mice dependent on activating FAK, as confirmed by combined use with FAK inhibitor. In summary, arctigenin can directly promote mucosal healing in colitis mice through facilitating focal adhesion turnover, especially assembly, and consequent migration of epithelial cells via targeting FAK. Arctigenin may be developed as a mucosal healing promoter, and FAK is a potential therapeutic target for UC and other mucosal defect-related diseases.

Preterm Birth and Infantile Appendicitis.

OBJECTIVE: To investigate the potential association between preterm birth and infantile appendicitis. METHODS: We conducted a retrospective, multicenter, matched case-control study. This study included consecutive patients <1 year of age with surgery- or autopsy-confirmed appendicitis, admitted between December 2007 and May 2023. For each case, 10 healthy infants were randomly selected and matched by age. Infants were categorized as neonates (0 to 28 days) or older infants (>28 days and <1 year). RESULTS: The study included 106 infants diagnosed with appendicitis (median age 2.4 months) and 1060 age-matched healthy controls. In the univariate analysis, preterm birth was significantly associated with the development of appendicitis within the first year of life (odds ratio [OR], 4.23; 95% confidence interval [CI], 2.67-6.70). Other factors associated with a higher risk of infantile appendicitis included being male (OR, 1.91; 95%CI, 1.25-2.94), weight-for-age z-score (OR, 0.72; 95%CI, 0.64-0.81), and exclusively fed on formula (OR, 2.95; 95%CI, 1.77-4.91). In multivariable analyses, preterm remained significantly associated with appendicitis (adjusted OR, 3.32; 95%CI, 1.76-6.24). Subgroup analysis revealed that a preterm birth history increased the risk of appendicitis in both neonates (adjusted OR, 4.56; 95%CI, 2.14-9.71) and older infants (adjusted OR, 3.63; 95%CI, 1.72-7.65). However, preterm did not significantly influence the incidence of appendiceal perforation. CONCLUSIONS: Preterm infants have an increased risk of appendicitis during the first year of life. A preterm birth history may help improve the timely diagnosis of infantile appendicitis.

Essential procedures of single-cell RNA sequencing in multiple myeloma and its translational value.

Multiple myeloma (MM) is a malignant neoplasm characterized by clonal proliferation of abnormal plasma cells. In many countries, it ranks as the second most prevalent malignant neoplasm of the hematopoietic system. Although treatment methods for MM have been continuously improved and the survival of patients has been dramatically prolonged, MM remains an incurable disease with a high probability of recurrence. As such, there are still many challenges to be addressed. One promising approach is single-cell RNA sequencing (scRNA-seq), which can elucidate the transcriptome heterogeneity of individual cells and reveal previously unknown cell types or states in complex tissues. In this review, we outlined the experimental workflow of scRNA-seq in MM, listed some commonly used scRNA-seq platforms and analytical tools. In addition, with the advent of scRNA-seq, many studies have made new progress in the key molecular mechanisms during MM clonal evolution, cell interactions and molecular regulation in the microenvironment, and drug resistance mechanisms in target therapy. We summarized the main findings and sequencing platforms for applying scRNA-seq to MM research and proposed broad directions for targeted therapies based on these findings.

Research on dynamic response characteristics of normal fault footwall working face and rock burst prevention technology under the influence of the gob area.

To study the effect of mining dynamic response characteristics on the footwall working face of the normal fault under the influence of the gob area, theoretical research, indoor experiment, and numerical simulation are adopted to analyze the stress manifestation characteristics, overburden movement, and energy evolution characteristics during the process of mining. The results show that: (1) In the process of mining toward the fault, the working face shows the change characteristics of "stable-activation mutation-final stability". At 20 m from the fault, the arch structure of the working face was damaged, fissures appeared near the high fault fracture zone, and the displacement of the overburden rock increased significantly; (2) the maximum value was reached at 4-8 m from the coal wall, and the superposition of tectonic stress and mining stress led to the concentration of the stress and energy accumulating on the top plate near the fault, and the data close to the gob area were even larger; (3) If the plastic damage zone of the high-level rock layer on the hanging wall and footwall of the fault appears to have a wide range of penetration, and the area formed between the shear displacement curve of the fault plane and the X-axis appears to have a significant enhancement, it is considered that the fault has been activated; (4) The size of the coal pillar of the fault is determined to be 40 m, and combined with the pressure unloading technique of the variable-diameter drilling hole, the validation is carried out through the micro-vibration monitoring, and the results of which can be used as a reference for the safety of the working face under similar conditions.

Integrating bulk and single-cell RNA sequencing data to establish necroptosis-related lncRNA risk model and analyze the immune microenvironment in hepatocellular carcinoma.

Background: The increasing evidence suggests that necroptosis mediates many behaviors of tumors, as well as the regulation of the tumor microenvironment. Long non-coding RNAs (lncRNAs) are involved in a variety of regulatory processes during tumor development and are significantly associated with patient prognosis. It suggests that necroptosis-related lncRNAs (NRlncRNAs) may serve as biomarkers for the prognosis of hepatocellular carcinoma (HCC). Methods: lncRNA expression profiles of HCC were obtained from TCGA database. LncRNAs associated with necroptosis were extracted using correlation analysis. Prognostic models were constructed based on least absolute shrinkage and selection operator algorithm (LASSO) and multivariate Cox regression analysis. The differences of tumor microenvironment between high-risk and low-risk groups were further analyzed. Single-cell RNA sequencing data of HCC was performed to assess the enrichment of necroptosis-related genes in immune cell subsets. Finally, real-time RT-PCR was used to detect the prognosis-related lncRNAs expression in different HCC cell lines. Results: We constructed a prognostic signature based on 8 NRlncRNAs, which also showed good predictive accuracy. The model showed that the prognosis of patients with high-risk score was significantly worse than that of patients with low-risk score (P < 0.05). Combined with the clinical characteristics and risk score of HCC, Nomogram was drawn for reference in clinical practice. In addition, immune cell infiltration analysis and single cell RNA sequencing analysis showed that a low level of immune infiltration was observed in patients at high risk and that there was a significant correlation between NRlncRNAs and macrophages. The results of RT-qPCR also showed that 8 necroptosis-related lncRNAs were highly expressed in HCC cell lines and human liver cancer tissues. Conclusion: This prognostic signature based on the necroptosis-related lncRNAs may provide meaningful clinical insights for the prognosis and immunotherapy responses in patients with HCC.