Ultra-High-Density Ferroelectric Array Formed by Sliding Ferroelectric Moiré Superlattices.

2D van der Waals (vdW) materials offer infinite possibilities for constructing unique ferroelectrics through simple layer stacking and rotation. In this work, we stack nonferroelectric GeS2 and ferroelectric CuInP2S6 to form heterostructures by combining sliding ferroelectric polarization with displacement ferroelectric polarization to achieve multiple polarization states. First-principles calculations reveal that the polarization reversal of the CuInP2S6 component in the GeS2/CuInP2S6/GeS2 heterostructure can simultaneously drive the switching of sliding ferroelectric polarization, displaying a robust coupling of the two polarizations and leading to the overall polarization switching. Based on this, ferroelectric arrays with a density of 6.55 × 1012 cm-2 (equivalent to a storage density of 0.7 TB cm-2) were constructed in a moiré superlattice, and the polarization strength of array elements was 11.77 pC/m, higher than that of all reported 2D vdW out-of-plane ferroelectrics. High density, large polarization, and electrically switchable array elements in ferroelectric arrays provide unprecedented opportunities to design 2D high-density nonvolatile ferroelectric memories.

Impact of Infection Patterns on the Outcomes of Patients with Hematological Malignancies in Southwest China: A 10-Year Retrospective Case-Control Study.

Background: This study aimed to assess the effect of infection patterns on the outcomes of patients with hematological malignancies (HM) and to identify the determinants of in-hospital mortality. Methods: A case-control study was retrospectively conducted in a tertiary teaching hospital in Chongqing, Southwest China from 2011 to 2020. Clinical characteristics, microbial findings, and outcomes of HM patients with infections were retrieved from the hospital information system. Chi-square or Fisher's exact test was adopted to test the significance of mortality rate. Kaplan-Meier survival analysis and Log rank test were applied to evaluate and compare the 30-day survival rates of those groups. Binary logistic regression, Cox proportional hazards regression, and receiver operating characteristic curves were used to investigate the determinants of in-hospital mortality. Results: Of 1,570 enrolled participants, 43.63% suffered from acute myeloid leukemia, 69.62% received chemotherapy, and 25.73% had hematopoietic stem cell transplantation (HSCT). Microbial infection was documented in 83.38% of participants. Co-infection and septic shock were reported in 32.87% and 5.67% of participants, respectively. Patients with septic shock suffered a significantly lower 30-day survival rate, while those with distinct types of pathogens or co-infections had a comparable 30-day survival rate. The all-cause in-hospital mortality was 7.01% and higher mortality rate was observed in patients with allo-HSCT (7.20%), co-infection (9.88%), and septic shock (33.71%). Cox proportional hazards regression illustrated that elderly age, septic shock, and elevated procalcitonin (PCT) were independent predictors of in-hospital mortality. A PCT cut-off value of 0.24 ng/mL predicted in-hospital mortality with a sensitivity of 77.45% and a specificity of 59.80% (95% CI = 0.684-0.779, P<0.0001). Conclusion: Distinct infectious patterns of HM inpatients were previously unreported in Southwest China. It was the severity of infection, not co-infection, source of infection, or type of causative pathogen that positively related to poor outcome. PCT guided early recognition and treatment of septic shock were advocated.

Point-of-care detection of Neisseria gonorrhoeae based on RPA-CRISPR/Cas12a.

Gonorrhea, caused by Neisseria gonorrhoeae (N. gonorrhoeae), is a persistent global public health threat. The development of low-cost, point-of-care testing is crucial for gonorrhea control, especially in regions with limited medical facilities. In this study, we integrated CRISPR/Cas12a reaction with recombinase polymerase amplification (RPA) to provide a simple and adaptable molecular detection method for N. gonorrhoeae. The RPA-Cas12a-based detection system developed in this study enables rapid detection of N. gonorrhoeae within 1 h without the use of specialized equipment. This method is highly specific for identifying N. gonorrhoeae without cross-reactivity with other prevalent pathogens. Furthermore, in the evaluation of 24 clinical samples, the detection system demonstrates a 100% concordance rate with traditional culture, which is being used clinically as a reference method. Overall, the RPA-Cas12a-based N. gonorrhoeae detection has the advantages of rapidity, portability, low-cost, no special equipment required, and strong operability, and has a high potential for application as a self-testing and point-of-care diagnosis, which is critical for the clinical management of gonorrhea in developing countries lacking medical equipment.

Corrigendum to "Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes (imPODs)" [Genes & Diseases 5 (2018) 137-149].

[This corrects the article DOI: 10.1016/j.gendis.2018.04.003.].

Corrigendum to "The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs" [Genes & Diseases 5 (2018) 62-74].

[This corrects the article DOI: 10.1016/j.gendis.2018.02.001.].

Corrigendum to "Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference" [Genes & Diseases 5(2018):172-184].

[This corrects the article DOI: 10.1016/j.gendis.2018.04.006.].

Cas12a/Guide RNA-Based Platforms for Rapidly and Accurately Identifying Staphylococcus aureus and Methicillin-Resistant S. aureus.

In order to ensure the prevention and control of methicillin-resistant Staphylococcus aureus (MRSA) infection, rapid and accurate detection of pathogens and their resistance phenotypes is a must. Therefore, this study aimed to develop a fast and precise nucleic acid detection platform for identifying S. aureus and MRSA. We initially constructed a CRISPR-Cas12a detection system by designing single guide RNAs (sgRNAs) specifically targeting the thermonuclease (nuc) and mecA genes. To increase the sensitivity of the CRISPR-Cas12a system, we incorporated PCR, loop-mediated isothermal amplification (LAMP), and recombinase polymerase amplification (RPA). Subsequently, we compared the sensitivity and specificity of the three amplification methods paired with the CRISPR-Cas12a system. Finally, the clinical performance of the methods was tested by analyzing the fluorescence readout of 111 clinical isolates. In order to visualize the results, lateral-flow test strip technology, which enables point-of-care testing, was also utilized. After comparing the sensitivity and specificity of three different methods, we determined that the nuc-LAMP-Cas12a and mecA-LAMP-Cas12a methods were the optimal detection methods. The nuc-LAMP-Cas12a platform showed a limit of detection (LOD) of 10 aM (~6 copies µL-1), while the mecA-LAMP-Cas12a platform demonstrated a LOD of 1 aM (~1 copy µL-1). The LOD of both platforms reached 4 × 103 fg/µL of genomic DNA. Critical evaluation of their efficiencies on 111 clinical bacterial isolates showed that they were 100% specific and 100% sensitive with both the fluorescence readout and the lateral-flow readout. Total detection time for the present assay was approximately 80 min (based on fluorescence readout) or 85 min (based on strip readout). These results indicated that the nuc-LAMP-Cas12a and mecA-LAMP-Cas12a platforms are promising tools for the rapid and accurate identification of S. aureus and MRSA. IMPORTANCE The spread of methicillin-resistant Staphylococcus aureus (MRSA) poses a major threat to global health. Isothermal amplification combined with the trans-cleavage activity of Cas12a has been exploited to generate diagnostic platforms for pathogen detection. Here, we describe the design and clinical evaluation of two highly sensitive and specific platforms, nuc-LAMP-Cas12a and mecA-LAMP-Cas12a, for the detection of S. aureus and MRSA in 111 clinical bacterial isolates. With a limit of detection (LOD) of 4 × 103 fg/µL of genomic DNA and a turnaround time of 80 to 85 min, the present assay was 100% specific and 100% sensitive using either fluorescence or the lateral-flow readout. The present assay promises clinical application for rapid and accurate identification of S. aureus and MRSA in limited-resource settings or at the point of care. Beyond S. aureus and MRSA, similar CRISPR diagnostic platforms will find widespread use in the detection of various infectious diseases, malignancies, pharmacogenetics, food contamination, and gene mutations.

Two CRISPR/Cas12a-based methods for fast and accurate detection of single-base mutations.

Current single-base mutation detection approaches are time-consuming, labor-intensive, and costly. This highlights the critical need for speedy and accurate technology capable of detecting single-base alterations. Using clustered regularly interspaced short palindromic repeats/associated protein 12a (CRISPR/Cas12a), two fundamental approaches for getting 100% differentiation of single-base mutations have been established, by which fluorescence signals could be detected for variants but not for wild strains. The first method required both polymerase chain reaction (PCR) and CRISPR/Cas12a cleavage: By introducing a mismatched base at the 3' end of the primers and adjusting the PCR settings, the wild strain strand amplifications were completely blocked prior to CRISPR/Cas12a cleavage. The parameters for Method 1 (PCR + CRISPR/Cas12a) could be easily controlled and adjusted to attain a sensitivity of one copy (about 6 copies µL-1). The second method included isothermal recombinase polymerase amplification (RPA) and CRISPR/Cas12a cleavage: By introducing an extra mismatched base adjacent to the single-base mutant site by RPA (IMAS-RPA), the RPA products from the wild strains were rendered incapable of triggering the cleavage activity of CRISPR/Cas12a. Method 2 (IMAS-RPA) was rapid and easy to implement (can be finished within 1 h). Because each method has its own set of advantages, the laboratory environment-appropriate methods can be selected independently. Both approaches are expected to aid in clinical diagnosis to some extent in the near future.

[Retracted] MicroRNA­18b acts as an oncogene in gastric cancer by directly targeting Kruppel­like factor 6.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Fig. 2C were strikingly similar to data that had appeared in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 1926­1934, 2019; DOI: 10.3892/mmr.2019.9830].

Differences in the Distribution of Species, Carbapenemases, Sequence Types, Antimicrobial Heteroresistance and Mortality Rates Between Pediatric and Adult Carbapenemase-Producing Enterobacterales in Bloodstream Infections.

The dissemination of carbapenemase-producing Enterobacterales (CPE) is worrisome given their scarce treatment options. CPE bloodstream infections (BSIs) had a high mortality rate in adults, and there was little data on pediatric CPE-BSIs around the world. We comprehensively explored the differences in the clinical and microbiological characteristics between pediatric and adult CPE-BSIs. Forty-eight pediatric and 78 adult CPE-BSIs cases were collected. All-cause 30 day-mortality in children with CPE-BSIs (14.6%, 7/48) was significantly lower than that in adult patients (42.3%, 33/78, p = 0.001). The subgroup in adults empirically treated with tigecycline as an active drug displayed a significantly higher 30-days crude mortality (63.3%, 19/30) than the subgroup treated without tigecycline (29.2%, 14/48, p = 0.003). K. pneumoniae was the most prevalent species in both the pediatric (45.8%, 22/48) and adult populations (64.1%, 50/78), with discrepant carbapenemase genes in each population: 95.4% (21/22) of the pediatric K. pneumoniae isolates carried bla NDM, while 82.0% (41/50) of the adult strains harbored bla KPC. The ratio of E. coli in children (37.5%) was significantly higher than that in adults (12.8%, p = 0.002). In both populations, the majority of E. coli expressed bla NDM, particularly bla NDM-5. With statistical significance, bla NDM was much more common in children (95.8%, 46/48) than in adults (34.6%, 27/78). The rate of multiple-heteroresistance phenotypes in children was as high as 87.5%, which was much lower in adults (57.1%). Agar dilution checkboard experiment against one pediatric carbapenemase-producing E. coli isolates showed that the combination of amikacin and fosfomycin yielded an additive effect. Overall, K. pneumoniae was the most common CPE-BSIs pathogen in both populations, with NDM-producing K. pneumoniae and KPC-producing ST11 K. pneumoniae being the most prevalent species in children and adults, respectively. E. coli was more prevalent in children than in adults, yet bla NDM-5 was the most common carbapenem-resistant mechanism in E. coli in both populations. The wide range of multiple-heteroresistance combination traits found in different pathogen species from different host populations should provide a good foundation for future combination therapy design. Further investigations from more CPE isolates of various species are needed to evaluate the possible in vitro partial synergy of the amikacin and fosfomycin combination.

Excellent Energy Storage Performance in Bi(Fe0.93Mn0.05Ti0.02)O3 Modified CaBi4Ti4O15 Thin Film by Adjusting Annealing Temperature.

Dielectric capacitors with ultrahigh power density are highly desired in modern electrical and electronic systems. However, their comprehensive performances still need to be further improved for application, such as recoverable energy storage density, efficiency and temperature stability. In this work, new lead-free bismuth layer-structured ferroelectric thin films of CaBi4Ti4O15-Bi(Fe0.93Mn0.05Ti0.02)O3 (CBTi-BFO) were prepared via chemical solution deposition. The CBTi-BFO film has a small crystallization temperature window and exhibits a polycrystalline bismuth layered structure with no secondary phases at annealing temperatures of 500-550 °C. The effects of annealing temperature on the energy storage performances of a series of thin films were investigated. The lower the annealing temperature of CBTi-BFO, the smaller the carrier concentration and the fewer defects, resulting in a higher intrinsic breakdown field strength of the corresponding film. Especially, the CBTi-BFO film annealed at 500 °C shows a high recoverable energy density of 82.8 J·cm-3 and efficiency of 78.3%, which can be attributed to the very slim hysteresis loop and a relatively high electric breakdown strength. Meanwhile, the optimized CBTi-BFO film capacitor exhibits superior fatigue endurance after 107 charge-discharge cycles, a preeminent thermal stability up to 200 °C, and an outstanding frequency stability in the range of 500 Hz-20 kHz. All these excellent performances indicate that the CBTi-BFO film can be used in high energy density storage applications.

Prognostic effect of lncRNA SNHG7 on cancer outcome: a meta and bioinformatic analysis.

BACKGROUND: New evidence from clinical and fundamental researches suggests that SNHG7 is involved in the occurrence and development of carcinomas. And the increased levels of SNHG7 are associated with poor prognosis in various kinds of tumors. However, the small sample size was the limitation for the prognostic value of SNHG7 in clinical application. The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of SNHG7 in various cancers. METHODS: Articles related to the SNHG7 as a prognostic biomarker for cancer patients, were comprehensive searched in several electronic databases. The enrolled articles were qualified via the preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology checklists. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was further used to validate our results. RESULTS: We analyzed 2418 cancer patients that met the specified criteria. The present research indicated that an elevated SNHG7 expression level was significantly associated with unfavorable overall survival (OS) (HR = 2.45, 95% CI: 2.12-2.85, p <0.001). Subgroup analysis showed that high expression levels of SNHG7 were also significantly associated with unfavorable OS in digestive system cancer (HR = 2.31, 95% CI: 1.90-2.80, p <0.001) and non-digestive system cancer (HR = 2.67, 95% CI: 2.12-3.37, p <0.001). Additionally, increased SNHG7 expression was found to be associated with tumor stage and progression (III/IV vs. I/II: HR = 1.76, 95% CI: 1.57-1.98, p <0.001). Furthermore, elevated SNHG7 expression significantly predicted lymph node metastasis (LNM) (HR = 1.98, 95% CI: 1.74-2.26, p <0.001) and distant metastasis (DM) (HR = 2.49, 95% CI: 1.88-3.30, p <0.001) respectively. No significant heterogeneity was observed among these studies. SNHG7 was significantly upregulated in four cancers and the elevated expression of SNHG7 predicted shorter OS in four cancers, worse DFS in five malignancies and worse PFI in five carcinomas based on the validation using the GEPIA on-line analysis tool. CONCLUSIONS: The present analysis suggests that elevated SNHG7 is significantly associated with unfavorable OS, tumor progression, LNM and DM in various carcinomas, and may be served as a promising biomarker to guide therapy for cancer patients.

In Vitro Activity of Auranofin in Combination With Aztreonam-Avibactam Against Metallo-ß-lactamase (MBL)-Producing Enterobacterales.

Objectives: To assess the efficacy of aztreonam-avibactam-auranofin (ATM-AVI-AUR) against a collection of 88 carbapenemase-producing Enterobacterales (CPE) clinical isolates and 6 in vitro selected ATM-AVI-resistant CPE with CMY-16 Tyr150Ser and Asn346His mutants or transformants. Methods: MICs of imipenem, ceftazidime-avibact8am (CAZ-AVI), ATM-AVI, CAZ-AVI-AUR and ATM-AVI-AUR were determined via the broth microdilution method. Genetic background and carbapenemase genes were determined by PCR and Sanger sequencing. Results: AUR alone showed little antibacterial activity with AUR MICs were greater than 64 µg/mL for all the 88 clinical CPE isolates. The addition of AUR (16 µg/mL) resulted in an 3-folding dilutions MIC reduction of ATM-AVI MIC50 (0.5 to 0.0625 µg/mL) and a 2-folding dilutions MIC reduction of MIC90 (1 to 0.25 µg/mL) against all 88 clinical CPE isolates, respectively. Notably, the reduced ATM-AVI MIC values were mainly found in MBL-producers, and the MIC50 and MIC90 reduced by 2-folding dilutions (0.25 to 0.0625 µg/mL) and 3-folding dilutions (2 to 0.25 µg/mL) respectively by AUR among the 51 MBL-producers. By contrast, the addition of AUR did not showed significant effects on ATM-AVI MIC50 (0.0625 µg/mL) and MIC90 (0.125 µg/mL) among single KPC-producers. Interestingly, the addition of AUR restored the ATM-AVI susceptibility against the 6 in vitro selected ATM-AVI-resistant CMY-16 Tyr150Ser and Asn346His mutants or transfromants, with the MICs reduced from ≥32 µg/mL (32->256 µg/mL) to ≤8 µg/mL (0.0625-8 µg/mL). Conclusions: Our results demonstrated that AUR potentiated the activities of CAZ-AVI and ATM-AVI against MBL-producing isolates in vitro. Importantly, AUR restored the ATM-AVI activity against ATM-AVI resistant mutant strains. As a clinically approved drug, AUR might be repurposed in combination with ATM-AVI to treat infections caused by highly resistant MBL-producing Enterobacterales.

The Pathogenic Role of Long Non-coding RNA H19 in Atherosclerosis via the miR-146a-5p/ANGPTL4 Pathway.

The abnormally expressed long non-coding RNA (lncRNA) H19 has a crucial function in the development and progression of cardiovascular disease; however, its role in atherosclerosis is yet to be known. We aimed to examine the impacts of lncRNA H19 on atherogenesis as well as the involved mechanism. The outcomes from this research illustrated that the expression of lncRNA H19 was elevated in mouse blood and aorta with lipid-loaded macrophages and atherosclerosis. Adeno-associated virus (AAV)-mediated lncRNA H19 overexpression significantly increased the atherosclerotic plaque area in apoE-/- mice supplied with a Western diet. The upregulation of lncRNA H19 decreased the miR-146a-5p expression but increased the levels of ANGPTL4 in mouse blood and aorta and THP-1 cells. Furthermore, lncRNA H19 overexpression promoted lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-induced THP-1 macrophages. However, the knockdown of lncRNA H19 served as a protection against atherosclerosis in apoE-/- mice and lowered the accumulation of lipids in ox-LDL-induced THP-1 macrophages. lncRNA H19 promoted the expression of ANGPTL4 via competitively binding to miR-146a-5p, thus promoting lipid accumulation in atherosclerosis. These findings altogether demonstrated that lncRNA H19 facilitated the accumulation of lipid in macrophages and aggravated the progression of atherosclerosis through the miR-146a-5p/ANGPTL4 pathway. Targeting lncRNA H19 might be an auspicious therapeutic approach for preventing and treating atherosclerotic disease.

Enhanced Ferroelectric, Dielectric Properties of Fe-Doped PMN-PT Thin Films.

Fe-doped 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-PT) thin films were grown in Pt/Ti/SiO2/Si substrate by a chemical solution deposition method. Effects of the annealing temperature and doping concentration on the crystallinity, microstructure, ferroelectric and dielectric properties of thin film were investigated. High (111) preferred orientation and density columnar structure were achieved in the 2% Fe-doped PMN-PT thin film annealed at 650 °C. The preferred orientation was transferred to a random orientation as the doping concentration increased. A 2% Fe-doped PMN-PT thin film showed the effectively reduced leakage current density, which was due to the fact that the oxygen vacancies were effectively restricted and a transition of Ti4+ to Ti3+ was prevented. The optimal ferroelectric properties of 2% Fe-doped PMN-PT thin film annealed at 650 °C were identified with slim polarization-applied field loops, high saturation polarization (Ps = 78.8 µC/cm2), remanent polarization (Pr = 23.1 µC/cm2) and low coercive voltage (Ec = 100 kV/cm). Moreover, the 2% Fe-doped PMN-PT thin film annealed at 650 °C showed an excellent dielectric performance with a high dielectric constant (εr ~1300 at 1 kHz).

Clinical and Microbiological Characterization of Carbapenem-Resistant Enterobacteriales: A Prospective Cohort Study.

Aim: We aim to depict the clinicoepidemiological and molecular information of carbapenem-resistant Enterobacteriales (CRE) in Chongqing, China. Methods: We performed a prospective, observational cohort study, recruiting inpatients diagnosed with CRE infections from June 1, 2018, to December 31, 2019. We carried out strain identification and molecular characterization of CRE. eBURST analysis was conducted to assess the relationships among the different isolates on the basis of their sequence types (STs) and associated epidemiological data using PHYLOViZ. Clinical parameters were compared between the carbapenemase-producing Enterobacteriales (CPE) and non-CPE group. Findings: 128 unique CRE isolates from 128 patients were collected during the study period: 69 (53.9%) CPE and 59 (46.1%) non-CPE. The majority of CPE isolates were bla KPC-2 (56.5%), followed by bla NDM (39.1%) and bla IMP (5.8%). Klebsiella pneumoniae carbapenemase (KPC)-producing clonal group 11 Klebsiella pneumoniae (K. pneumoniae) was the most common CPE. Antibiotic resistance was more frequent in the CPE group than in the non-CPE group. Independent predictors for CPE infection were ICU admission and hepatobiliary system diseases. Although, there was no significant difference in desirability of outcome ranking (DOOR) outcomes between the two groups. At 30 days after index culture, 35 (27.3% ) of these patients had died. Conclusion: CRE infections were related to high mortality and poor outcomes, regardless of CRE subgroups. CPE were associated with prolonged ICU stays and had different clinical and microbiological characteristics than non-CPE. The identification of CPE/non-CPE and CRE resistance mechanisms is essential for better guidance of the clinical administration of patients with CRE infections.

LncRNAs as Therapeutic Targets and Potential Biomarkers for Lipid-Related Diseases.

Lipid metabolism is an essential biological process involved in nutrient adjustment, hormone regulation, and lipid homeostasis. An irregular lifestyle and long-term nutrient overload can cause lipid-related diseases, including atherosclerosis, myocardial infarction (MI), obesity, and fatty liver diseases. Thus, novel tools for efficient diagnosis and treatment of dysfunctional lipid metabolism are urgently required. Furthermore, it is known that lncRNAs based regulation like sponging microRNAs (miRNAs) or serving as a reservoir for microRNAs play an essential role in the progression of lipid-related diseases. Accordingly, a better understanding of the regulatory roles of lncRNAs in lipid-related diseases would provide the basis for identifying potential biomarkers and therapeutic targets for lipid-related diseases. This review highlighted the latest advances on the potential biomarkers of lncRNAs in lipid-related diseases and summarised current knowledge on dysregulated lncRNAs and their potential molecular mechanisms. We have also provided novel insights into the underlying mechanisms of lncRNAs which might serve as potential biomarkers and therapeutic targets for lipid-related diseases. The information presented here may be useful for designing future studies and advancing investigations of lncRNAs as biomarkers for diagnosis, prognosis, and therapy of lipid-related diseases.

Targeting epigenetics and lncRNAs in liver disease: From mechanisms to therapeutics.

Early onset and progression of liver diseases can be driven by aberrant transcriptional regulation. Different transcriptional regulation processes, such as RNA/DNA methylation, histone modification, and ncRNA-mediated targeting, can regulate biological processes in healthy cells, as well also under various pathological conditions, especially liver disease. Numerous studies over the past decades have demonstrated that liver disease has a strong epigenetic component. Therefore, the epigenetic basis of liver disease has challenged our knowledge of epigenetics, and epigenetics field has undergone an important transformation: from a biological phenomenon to an emerging focus of disease research. Furthermore, inhibitors of different epigenetic regulators, such as m6A-related factors, are being explored as potential candidates for preventing and treating liver diseases. In the present review, we summarize and discuss the current knowledge of five distinct but interconnected and interdependent epigenetic processes in the context of hepatic diseases: RNA methylation, DNA methylation, histone methylation, miRNAs, and lncRNAs. Finally, we discuss the potential therapeutic implications and future challenges and ongoing research in the field. Our review also provides a perspective for identifying therapeutic targets and new hepatic biomarkers of liver disease, bringing precision research and disease therapy to the modern era of epigenetics.

Potential Therapeutic Targeting of lncRNAs in Cholesterol Homeostasis.

Maintaining cholesterol homeostasis is essential for normal cellular and systemic functions. Long non-coding RNAs (lncRNAs) represent a mechanism to fine-tune numerous biological processes by controlling gene expression. LncRNAs have emerged as important regulators in cholesterol homeostasis. Dysregulation of lncRNAs expression is associated with lipid-related diseases, suggesting that manipulating the lncRNAs expression could be a promising therapeutic approach to ameliorate liver disease progression and cardiovascular disease (CVD). However, given the high-abundant lncRNAs and the poor genetic conservation between species, much work is required to elucidate the specific role of lncRNAs in regulating cholesterol homeostasis. In this review, we highlighted the latest advances in the pivotal role and mechanism of lncRNAs in regulating cholesterol homeostasis. These findings provide novel insights into the underlying mechanisms of lncRNAs in lipid-related diseases and may offer potential therapeutic targets for treating lipid-related diseases.