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.

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.

Avibactam potentiated the activity of both ceftazidime and aztreonam against S. maltophilia clinical isolates in vitro.

BACKGROUND: Treatment options for Stenotrophomonas maltophilia (S. maltophilia) infections were limited. We assessed the efficacy of ceftazidime (CAZ), ceftazidime-avibactam (CAZ-AVI), aztreonam (ATM), and aztreonam-avibactam (ATM-AVI) against a selection of 76 S. maltophilia out of the 1179 strains isolated from the First Affiliated Hospital of Chongqing Medical University during 2011-2018. METHODS: We investigated the antimicrobial resistance profiles of the 1179 S. maltophilia clinical isolates from the first affiliated hospital of Chongqing Medical University during 2011-2018, a collection of 76 isolates were selected for further study of microbiological characterization. Minimum inhibitory concentrations (MICs) of CAZ, CAZ-AVI, ATM and ATM-AVI were determined via the broth microdilution method. We deemed that CAZ-AVI or ATM-AVI was more active in vitro than CAZ or ATM alone when CAZ-AVI or ATM-AVI led to a category change from "Resistant" or "Intermediate" with CAZ or ATM alone to "Susceptible" with CAZ-AVI or ATM-AVI, or if the MIC of CAZ-AVI or ATM-AVI was at least 4-fold lower than the MIC of CAZ or ATM alone. RESULTS: For the 76 clinical isolates included in the study, MICs of CAZ, ATM, CAZ-AVI and ATM-AVI ranged from 0.03-64, 1-1024, 0.016-64, and 0.06-64 µg/mL, respectively. In combined therapy, AVI was active at restoring the activity of 48.48% (16/33) and 89.71% (61/68) of S. maltophilia to CAZ and ATM, respectively. Furthermore, CAZ-AVI showed better results in terms of the proportion of susceptible isolates (77.63% vs. 56.58%, P < 0.001), and MIC50 (2 µg/mL vs. 8 µg/mL, P < 0.05) when compared to CAZ. According to our definition, CAZ-AVI was more active in vitro than CAZ alone for 81.58% (62/76) of the isolates. Similarly, ATM-AVI also showed better results in terms of the proportion of susceptible isolates (90.79% vs.10.53%, P < 0.001) and MIC50 (2 µg/mL vs. 64 µg/mL, P < 0.001) when compared to ATM. According to our definition, ATM-AVI was also more active in vitro than ATM alone for 94.74% (72/76) of the isolates. CONCLUSIONS: AVI potentiated the activity of both CAZ and ATM against S. maltophilia clinical isolates in vitro. We demonstrated that CAZ-AVI and ATM-AVI are both useful therapeutic options to treat infections caused by S. maltophilia.

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.

Visualization of Aluminum Ions at the Mica Water Interface Links Hydrolysis State-to-Surface Potential and Particle Adhesion.

When hydrolyzable cations such as aluminum interact with solid-water interfaces, macroscopic interfacial properties (e.g., surface charge and potential) and interfacial phenomena (e.g., particle adhesion) become tightly linked with the microscopic details of ion adsorption and speciation. We use in situ atomic force microscopy to directly image individual aluminum ions at a mica-water interface and show how adsorbate populations change with pH and aluminum activity. Complementary streaming potential measurements then allow us to build a triple layer model (TLM) that links surface potentials to adsorbate populations, via equilibrium binding constants. Our model predicts that hydrolyzed species dominate the mica-water interface, even when unhydrolyzed species dominate the solution. Ab initio molecular dynamics (AIMD) simulations confirm that aluminum hydrolysis is strongly promoted at the interface. The TLM indicates that hydrolyzed adsorbates are responsible for surface-potential inversions, and we find strong correlations between hydrolyzed adsorbates and particle-adhesion forces, suggesting that these species mediate adhesion by chemical bridging.

BMP9-induced osteoblastic differentiation requires functional Notch signaling in mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into multiple lineages including osteoblastic lineage. Osteogenic differentiation of MSCs is a cascade that recapitulates most, if not all, of the molecular events occurring during embryonic skeletal development, which is regulated by numerous signaling pathways including bone morphogenetic proteins (BMPs). Through a comprehensive analysis of the osteogenic activity, we previously demonstrated that BMP9 is the most potent BMP for inducing bone formation from MSCs both in vitro and in vivo. However, as one of the least studied BMPs, the essential mediators of BMP9-induced osteogenic signaling remain elusive. Here we show that BMP9-induced osteogenic signaling in MSCs requires intact Notch signaling. While the expression of Notch receptors and ligands are readily detectable in MSCs, Notch inhibitor and dominant-negative Notch1 effectively inhibit BMP9-induced osteogenic differentiation in vitro and ectopic bone formation in vivo. Genetic disruption of Notch pathway severely impairs BMP9-induced osteogenic differentiation and ectopic bone formation from MSCs. Furthermore, while BMP9-induced expression of early-responsive genes is not affected by defective Notch signaling, BMP9 upregulates the expression of Notch receptors and ligands at the intermediate stage of osteogenic differentiation. Taken together, these results demonstrate that Notch signaling may play an essential role in coordinating BMP9-induced osteogenic differentiation of MSCs.

Reversibly immortalized human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are responsive to BMP9-induced osteogenic and adipogenic differentiation.

Human mesenchymal stem cells (MSCs) are a heterogeneous subset of nonhematopoietic multipotent stromal stem cells and can differentiate into mesodermal lineage, such as adipocytes, osteocytes, and chondrocytes, as well as ectodermal and endodermal lineages. Human umbilical cord (UC) is one of the most promising sources of MSCs. However, the molecular and cellular characteristics of UC-derived MSCs (UC-MSCs) require extensive investigations, which are hampered by the limited lifespan and the diminished potency over passages. Here, we used the piggyBac transposon-based simian virus 40 T antigen (SV40T) immortalization system and effectively immortalized UC-MSCs, yielding the iUC-MSCs. A vast majority of the immortalized lines are positive for MSC markers but not for hematopoietic markers. The immortalization phenotype of the iUC-MSCs can be effectively reversed by flippase recombinase-induced the removal of SV40T antigen. While possessing long-term proliferation capability, the iUC-MSCs are not tumorigenic in vivo. Upon bone morphogenetic protein 9 (BMP9) stimulation, the iUC-MSC cells effectively differentiate into osteogenic, chondrogenic, and adipogenic lineages both in vitro and in vivo, which is indistinguishable from that of primary UC-MSCs, indicating that the immortalized UC-MSCs possess the characteristics similar to that of their primary counterparts and retain trilineage differentiation potential upon BMP9 stimulation. Therefore, the engineered iUC-MSCs should be a valuable alternative cell source for studying UC-MSC biology and their potential utilities in immunotherapies and regenerative medicine.

Niclosamide Exhibits Potent Anticancer Activity and Synergizes with Sorafenib in Human Renal Cell Cancer Cells.

BACKGROUND/AIMS: As the most lethal urological cancers, renal cell carcinoma (RCC) comprises a heterogeneous group of cancer with diverse genetic and molecular alterations. There is an unmet clinical need to develop efficacious therapeutics for advanced, metastatic and/or relapsed RCC. Here, we investigate whether anthelmintic drug Niclosamide exhibits anticancer activity and synergizes with targeted therapy Sorafenib in suppressing RCC cell proliferation. METHODS: Cell proliferation and migration were assessed by Crystal violet staining, WST-1 assay, cell wounding and cell cycle analysis. Gene expression was assessed by qPCR. In vivo anticancer activity was assessed in xenograft tumor model. RESULTS: We find that Niclosamide effectively inhibits cell proliferation, cell migration and cell cycle progression, and induces apoptosis in human renal cancer cells. Mechanistically, Niclosamide inhibits the expression of C-MYC and E2F1 while inducing the expression of PTEN in RCC cells. Niclosamide is further shown to synergize with Sorafenib in suppressing RCC cell proliferation and survival. In the xenograft tumor model, Niclosamide is shown to effectively inhibit tumor growth and suppress RCC cell proliferation. CONCLUSIONS: Niclosamide may be repurposed as a potent anticancer agent, which can potentiate the anticancer activity of the other agents targeting different signaling pathways in the treatment of human RCC.

IL-17B is elevated in patients with pneumonia and mediates IL-8 production in bronchial epithelial cells.

The role of IL-17B in regulating pulmonary immunity and inflammation is unknown. In this study, we found that IL-17B concentrations were significantly elevated in adult and paediatric patients with community-acquired pneumonia relative to their corresponding healthy adult and paediatric controls. The increased concentrations of IL-17B significantly and positively correlated with chemokine IL-8 concentrations in clinical pneumonia. In vitro studies demonstrated that IL-17B could induce gene and protein expression of IL-8 in human bronchial epithelial cells, but not lung fibroblasts, which was regulated by the activation of Akt, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-κB) signaling pathways. In vivo studies further showed that increased IL-17B levels significantly and positively correlated with IL-8 concentrations in experimental pneumonia. In conclusion, human pneumonia was associated with enhanced release of IL-17B, which might regulate pulmonary immunity and inflammation through the induction of IL-8 in bronchial epithelial cells.

sTLR4/MD-2 complex inhibits colorectal cancer migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation.

Long non-coding RNAs (lncRNAs) have multiple functions in gene regulation and during cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC) have not yet been well understood. In our previous study, we demonstrated that sTLR4/MD-2 complex can inhibit CRC in vitro and in vivo by targeting LPS. Therefore, the aim of the present study is to investigate the expression of lncRNA H19 in CRC and to evaluate its effect on the inhibition of sTLR4/MD-2 complex. The expression of H19 is measured in 63 CRC tumor tissues and adjacent normal tissues by quantitative real-time PCR (qRT-PCR). The effects of H19 on migration and invasiveness are evaluated by wound healing assay, migration and invasion assays. Results showed that H19 is significantly overexpressed in cancerous tissues and CRC cell lines compared with adjacent normal tissues and a normal human intestinal epithelial cell line. Moreover, H19 overexpression is closely associated with CRC patients. Our in vitro data indicated that knockdown of H19 inhibits the migration and invasiveness of CRC cells. And in vivo sTLR4/MD-2 complex inhibits tumor growth in mice and the expression of H19 is down-regulated. These results suggest that sTLR4/MD-2 complex inhibits CRC migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation.

Cell-penetrating fusion peptides OD1 and OD2 interact with Bcr-Abl and influence the growth and apoptosis of K562 cells.

The Bcr-Abl oncoprotein is the cause of chronic myelogenous leukemia (CML). Crystal structure analysis suggests that Bcr30-63 is the core of the Bcr-Abl oligomerization interface for aberrant kinase activity; however, the precise role of other residues of Bcr1-72 excluding Bcr30-63 have not been evaluated. In this study, Bcr30-63 was named OD2 and other residues of Bcr1-72 were named OD1. Cytoplasmic transduction peptide (CTP) was used to carry molecules into cytoplasm. CTP-OD1 and CTP-OD2 fusion peptides were expressed from a cold-inducible expression system. Our results demonstrated that both fusion peptides could localize into the cytoplasm, specifically interact with the Bcr-Abl protein and further inhibit growth, induce apoptosis, and decrease the phosphorylation of Bcr-Abl in K562 cell lines. However, the viability of THP-1, a Bcr-Abl negative cell line, was unaffected. These results suggested that CTP-OD1 and CTP-OD2 may be an attractive therapeutic option to inhibit the activation of Bcr-Abl kinase in CML.

[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].

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.

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.

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.

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.

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.].

Characterization of hepatitis B virus molecular genotypes in Chongqing and quantitative serological markers in patients during natural phases of chronic hepatitis B infection.

BACKGROUND/AIMS: The present study was launched to systematically characterize the molecular genotypes and quantitative serological biomarkers during the natural course of chronic hepatitis B (CHB) infection in a patient population from Chongqing, China. METHODS: A total of 140 patients were enrolled and grouped according to the natural phases of HBV infection: HBeAg (+) immune tolerance, immune clearance, HBeAg (-) low replicative and reactivation phase. Nested PCR was used for HBV molecular genotyping and chemiluminescent microparticle immunoassay for quantitative serological detection. RESULTS: Subgenotypes B2 and C2 were found to be most prevalent with genotype B patients showing more potent viral activity. HBsAg level was found to be significantly correlated with HBV DNA, HBeAg, age, ALT and AST levels during some phases of CHB. CONCLUSION: These results indicated that molecular genotyping and quantitative serological detection might be helpful for earlier prediction of the long-term disease outcomes.