Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker.

BACKGROUND: DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far. METHODS: Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation. RESULTS: DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer. CONCLUSIONS: Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.

Regulating the Electronic Structure of Freestanding Graphene on SiC by Ge/Sn Intercalation: A Theoretical Study.

The intrinsic n-type of epitaxial graphene on SiC substrate limits its applications in microelectronic devices, and it is thus vital to modulate and achieve p-type and charge-neutral graphene. The main groups of metal intercalations, such as Ge and Sn, are found to be excellent candidates to achieve this goal based on the first-principle calculation results. They can modulate the conduction type of graphene via intercalation coverages and bring out interesting magnetic properties to the entire intercalation structures without inducing magnetism to graphene, which is superior to the transition metal intercalations, such as Fe and Mn. It is found that the Ge intercalation leads to ambipolar doping of graphene, and the p-type graphene can only be obtained when forming the Ge adatom between Ge layer and graphene. Charge-neutral graphene can be achieved under high Sn intercalation coverage (7/8 bilayer) owing to the significantly increased distance between graphene and deformed Sn intercalation. These findings would open up an avenue for developing novel graphene-based spintronic and electric devices on SiC substrate.

CXCL2 attenuates osteoblast differentiation by inhibiting the ERK1/2 signaling pathway.

The C-X-C motif chemokine ligand 2 (CXCL2), a member of the CXC receptor ligand family, is involved in various immune and inflammatory processes, but its effect(s) on bone formation have not yet been reported. We report here that CXCL2 is enriched in bone marrow and show abundant expression of CXCL2 in osteoblasts of osteoporotic mice. CXCL2 neutralization within the bone marrow by using antibody alleviated bone loss in mice, indicating a negative role of CXCL2 in bone formation. In line with this, CXCL2 overexpression attenuated proliferation, as well as differentiation, of osteoblasts in vitro By contrast, CXCL2 downregulation promoted osteoblast expansion and differentiation. Mechanistically, CXCL2 inhibits the ERK1/2 (MAPK3/1) signaling pathway in osteoblasts. Activation of ERK1/2 abolishes the inhibitory effect of CXCL2 in osteoblasts, whereas inactivation of ERK1/2 reverses the osteogenic role of CXCL2 inhibition. These results show that CXCL2 attenuates osteoblast differentiation through inhibition of the ERK1/2 signaling pathway. We demonstrate here that CXCL2 is a negative regulator of bone formation and clarify the responsible mechanisms. Therefore, pharmaceutical coordination of CXCL2 and of the pathways through which it is regulated in osteoblasts might be beneficial regarding bone formation.

The challenge of diagnosis and treatment of neurosyphilis in China: results from a nationwide survey.

Background The uncertainty of how neurosyphilis is diagnosed and treated in clinical settings led us to investigate whether this serious manifestation of syphilis infection is properly managed in China. METHODS: This national cross-sectional study of the diagnosis and treatment of neurosyphilis included 1392 clinicians at 398 hospitals located in 116 cities in China. RESULTS: Of 398 hospitals, 244 (61.3%) failed to perform diagnostic laboratory tests and 181 (45.5%) failed to provide recommended treatment for neurosyphilis. Of 1392 clinicians, 536 (38.5%) had previously diagnosed patients with neurosyphilis, but 419 (78.2%) of the latter provided diagnoses that did not meet the criteria set by national guidelines. Of the 485 clinicians who had previously treated patients with neurosyphilis, 280 (57.7%) failed to follow national guidelines for treatment. Analysis indicated that clinicians working in North China (adjusted odds ratio (aOR), 4.24; 95% confidence interval (CI), 1.65-10.88), tertiary hospitals (aOR, 3.23; 95% CI, 1.63-6.41), and hospitals specialising in sexually transmitted infections (aOR, 2.49; 95% CI, 1.24-4.99) were more likely to follow national guidelines for neurosyphilis treatment. CONCLUSION: Lack of knowledge in disease management poses a great obstacle to prevent the serious consequences of neurosyphilis in Chinese patients. More effective measures are urgently needed to improve this suboptimal situation.

MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), one of the first found cancer-associated long noncoding RNAs (lncRNAs), involves in the development and progression of many types of tumors. An aberrant expression of MALAT1 was observed in hepatocellular carcinoma, cervical cancer, breast cancer, ovarian cancer, and colorectal cancer. However, the exact effects and molecular mechanisms of MALAT1 in osteosarcoma progression are still unknown up to now. Here, we investigated the role of MALAT1 in human osteosarcoma cell lines and clinical tumor samples in order to determine the function of this molecule. In our research, the MALAT1 messenger RNA (mRNA) was highly expressed in human osteosarcoma tissues, and its expression level was closely correlated with pulmonary metastasis. Then, we employed lentivirus-mediated knockdown of MALAT1 in U-2 OS and SaO2 to determine the role of MALAT1 in osteosarcoma cell lines. Lentivirus-mediated MALAT1 small interfering RNA (siRNA) could efficiently downregulated the expression level of MALAT1 in osteosarcoma cell lines. Knockdown of MALAT1 inhibited the proliferation and invasion of human osteosarcoma cell and suppressed its metastasis in vitro and vivo. At the same time, the proliferating cell nuclear antigen (PCNA), matrix metallopeptidase 9 (MMP-9), phosphorylated PI3Kp85α, and Akt expressions were significantly inhibited in MALAT1-deleted cells. These findings indicated that MALAT1 might suppress the tumor growth and metastasis via PI3K/AKT signaling pathway. Taken together, our data indicated that MALAT1 might be an oncogenic lncRNA that promoted proliferation and metastasis of osteosarcoma and could be regarded as a therapeutic target in human osteosarcoma.

Association of sexually transmitted infections with high-risk human papillomavirus types: a survey with 802 female sex workers in china.

A cross-sectional study that investigated the association between cervical infection of Chlamydia trachomatis, Neisseria gonorrhoeae, or Mycoplasma genitalium and infection with high-risk types of human papillomavirus among female sex workers in China found that the presence of cervical C. trachomatis or M. genitalium infection was independently associated with infection with certain high-risk types of specific high-risk human papillomavirus among this population.

The prevalences of Neisseria gonorrhoeae and Chlamydia trachomatis infections among female sex workers in China.

BACKGROUND: Sexually transmitted infections (STIs) have become a major public health problem among female sex workers (FSWs) in China. There have been many studies on prevalences of HIV and syphilis but the data about Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections are limited in this population in China. METHODS: A cross-sectional study was performed among FSWs recruited from different types of venues in 8 cities in China. An interview with questionnaire was conducted, followed by collection of a blood and cervical swab specimens for tests of HIV, syphilis, NG and CT infections. RESULTS: A total of 3,099 FSWs were included in the study. The overall prevalence rates of HIV, syphilis, NG and CT were 0.26%, 6.45%, 5.91% and 17.30%, respectively. Being a FSW from low-tier venue (adjusted odds ratios [AOR]=1.39) had higher risk and being age of ≥ 21 years (AOR=0.60 for 21-25 years; AOR=0.29 for 26-30 years; AOR=0.35 for 31 years or above) had lower risk for CT infection; and having CT infection was significantly associated with NG infection. CONCLUSIONS: The high STI prevalence rates found among FSWs, especially among FSWs in low-tier sex work venues, suggest that the comprehensive prevention and control programs including not only behavioral interventions but also screening and medical care are needed to meet the needs of this population.

The effect of a structural intervention for syphilis control among 3597 female sex workers: a demonstration study in South China.

BACKGROUND: Syphilis has made a rapid resurgence in China, especially among high-risk groups including female sex workers (FSWs). METHODS: Two cities in each of 3 provinces in South China were chosen and allocated to intervention or control arms. The intervention consisted of enhancing community-based syphilis screening outreach intervention with comprehensive sexually transmitted infection services at designated clinics while the control maintained routine intervention activities. Generalized linear modeling was used to examine effect of the intervention on incident syphilis infection. RESULTS: A total of 8275 women were eligible, and 3597 women enrolled (n = 2011 in control arm, n = 1586 in intervention arm) in the study. The median follow-up duration was 375 days (interquartile range, 267­475). Syphilis incidence density in the intervention group was reduced by 70% (95% confidence interval, 53%­81%) compared with the incidence in the control arm. The syphilis prevention intervention benefits were robust among FSWs at low-tier venues, individuals with less than high school education, migrants, and women who did not report condom use during the last episode of sex. CONCLUSIONS: Integrated sexually transmitted infection and human immunodeficiency virus prevention strategies substantially reduce syphilis incidence among FSWs, especially among those at low-tier venues. This intervention suggests the need for scaling up comprehensive FSW programs in China.

Corrigendum: METTL3 contributes to osteosarcoma progression by increasing DANCR mRNA stability via m6A modification.

[This corrects the article DOI: 10.3389/fcell.2021.784719.].

Prevalence and genotype distribution of human papillomavirus infection among female sex workers in Guangxi, China: implications for interventions.

Human papillomavirus (HPV) infection is a major public health concern in women, but information on HPV among female sex workers in China is limited. The aim of the study was to estimate the prevalence and genotype distribution of HPV infection among female sex workers in two cities in Guangxi, China. A total of 811 female sex workers were recruited from venues between July and September of 2009. Data on socio-demographic and behavior characteristics were collected, and cervical swabs were collected to determine HPV infection and genotype distribution. The overall prevalence of infection with any HPV type was 38.9%. HPV type 52 was the most prevalent type with prevalence of 11%, followed by HPV types 16, 58, 53, and CP8304, with prevalences of 6.5%, 5.7%, 5.6%, and 4.8%, respectively. HPV 16 or 18 accounted for 23.2% of all HPV positive cases. Age group <20 years was significantly associated with infection of the high-risk and multiple types of HPV infection. A higher prevalence of multiple HPV infection was observed among female sex workers from the outdoor venues (14.0%; 95%CI, 10.6%-17.3%). These findings have important implications for developing HPV prevention programs including HPV vaccination in female sex workers.

Prevalence and risk factors of HSV-2 infection and HSV-2/HIV coinfection in men who have sex with men in China: a multisite cross-sectional study.

OBJECTIVES: To determine the prevalence and risk factors of herpes simplex virus type 2 (HSV-2) infection and its coinfection with human immunodeficiency virus (HIV) in men who have sex with men (MSM) in China. METHODS: A convenience sample of 1462 MSM were recruited from different settings (an STD clinic, a health center, and MSM venues) in 3 cities in China. Blood specimens were collected for testing for antibodies to HSV-2 and HIV to determinate the seroprevalence of HSV-2 infection and HSV-2/HIV coinfection. Information on sociodemographic and behavioral characteristics was collected to determine the risk factors associated with the infections. RESULTS: The prevalence of HSV-2 infection in 1462 MSM was 16.0% (95% confidence interval [CI], 14.2%-18.0%), the prevalence of HIV infection in this population was 9.5% (95% CI, 8.1%-11.1%), and the rate of coinfection of HSV-2 and HIV was 3.2% (95% CI, 2.4%-4.3%). Multivariate logistic regression analysis showed that risk factors for HSV-2 infection included age older than 30 years, education level lower than senior high school, involvement in commercial sex work, and HIV-positive status. Education level lower than junior high school and history of sexual abuse were associated with HSV-2/HIV coinfection. CONCLUSIONS: The high prevalence of HSV-2 infection and HSV-2/HIV coinfection among MSM in China suggests that an increased focus on HSV control is warranted within China's prevention and intervention programs targeted toward MSM.

HIV prevalence varies between female sex workers from different types of venues in southern China.

We conducted a cross-sectional study on prevalence of human immunodeficiency virus (HIV) and syphilis among female sex workers (FSWs) recruited from different types of venues in 6 cities in China. Among 5322 FSWs (1379 were from high-tier venues, 2482 from middle-tier venues, and 1461 from low-tier venues, respectively), overall HIV prevalence was 0.54% (95% confidence interval [CI], 0.37%- 0.76%). By typology of venues where FSWs solicited clients, the prevalence was 1.37% (95% CI, 0.89%-2.11%) in low-tier venues, 0.28% (95% CI, 0.14%- 0.58%) in middle-tier venues, and 0.07% (95% CI, 0.01%-0.41%) in high-tier venues. The final logistic regression model showed an association of having had HIV infection with working in low-tier venues (adjusted odds ratio 2.73; 95% CI, 1.12-6.67) and coming from Guangxi Province (adjusted odds ratio, 7.89; 95% CI, 1.65-37.64). It can be concluded that FSWs working in low-tier venues (on the streets or public outdoor places) had higher risk of HIV infection than other venues. Such subgroup of FSWs should be efficiently covered by the current HIV/STD surveillance and intervention programs in China.

Developing and piloting an expert system for better routine voluntary HIV counseling and testing in China: preliminary results and lessons.

This study aims at developing and testing a pragmatic expert system for HIV voluntary counseling (VCT-ES) that leverages best practices. The VCT-ES was developed via evolutionary prototyping and piloted in 10 voluntary HIV counseling and testing (VCT) clinics from Anhui and Beijing representative of prefecture and county level VCT clinics in China. All counselors with the clinics and the clients to the clinics within selected two weeks at baseline and the end of study were invited to participate. Assessment measures included essential counseling procedures (ECPs); clients' satisfaction, knowledge, and behavior efficacy. VCT-ES was developed which tries to model and facilitate standard VCT operation procedures and best practices. One hundred and eighty-two (96 at baseline vs. 86 after intervention) cases recordings, 172 (96 vs. 76) client questionnaires, 10 counselor, and 2 expert rating instruments were collected; and 17 clients and 8 counselors participated in qualitative interviews. VCT-ES increased delivery of ECPs from 18.94% to 66.39% on average; increased clients' knowledge from 40.51% to 86.34% and self-efficacy by 22.42%. The VCT-ES applications listed were rated 9.1 on average (maximum = 10). The VCT-ES could be an easy and effective solution to better routine VCT and merits further research.

Prevalence of syphilis infection in different tiers of female sex workers in China: implications for surveillance and interventions.

BACKGROUND: Syphilis has made a dramatic resurgence in China during the past two decades and become the third most prevalent notifiable infectious disease in China. Female sex workers (FSWs) have become one of key populations for the epidemic. In order to investigate syphilis infection among different tiers of FSWs, a cross-sectional study was conducted in 8 sites in China. METHODS: Serum specimens (n = 7,118) were collected to test for syphilis and questionnaire interviews were conducted to obtain socio-demographic and behavioral information among FSWs recruited from different types of venues. FSWs were categorized into three tiers (high-, middle- and low-tier FSWs) based on the venues where they solicited clients. Serum specimens were screened with enzyme-linked immunosorbent assay (ELISA) for treponemal antibody followed by confirmation with non-treponemal toluidine red unheated serum test (TRUST) for positive ELISA specimens to determine syphilis infection. A logistic regression model was used to determine factors associated with syphilis infection. RESULTS: Overall syphilis prevalence was 5.0% (95%CI, 4.5-5.5%). Low-tier FSWs had the highest prevalence (9.7%; 95%CI, 8.3-11.1%), followed by middle-tier (4.3%; 95%CI, 3.6-5.0%, P < 0.001) and high-tier FSWs (2.2%; 95%CI, 1.6-2.9%, P < 0.001). Factors independently associated with syphilis infection included older age, lower education level, geographic location, lower tier of typology, and injection drug use. CONCLUSIONS: This multi-site survey showed a high prevalence of syphilis infection among FSWs and substantial disparities in syphilis prevalence by the tier of FSWs. The difference in syphilis prevalence is substantial between different tiers of FSWs, with the highest rate among low-tier FSWs. Thus, current surveillance and intervention activities, which have low coverage in low-tier FSWs in China, should be further examined.

Risk factors for Mycoplasma genitalium infection among female sex workers: a cross-sectional study in two cities in southwest China.

BACKGROUND: Mycoplasma genitalium (MG) is one of the common causes of non-gonococcal urethritis (NGU) in men and is associated with cervicitis, endometritis, and pelvic inflammatory diseases (PID) in women. The prevalence of MG infection has been reported to be high among female sex workers (FSWs) in many countries, but limited information is known among this population in China. METHODS: From July to September 2009, venue-based FSWs were recruited in two cities (Wuzhou and Hezhou) of Guangxi Autonomous Region in southwest China. Information of socio-demographic and behavioral characteristics was collected by a questionnaire-based interview. Cervical specimens were obtained for detection of MG using a real-time polymerase chain reaction (PCR) assay targeting mgpA gene. RESULTS: The overall prevalence of MG infection among 810 FSWs was 13.2% (95% CI = 10.87%-15.52%). MG infection was significantly associated with less education (adjusted odds ratio (AOR) = 2.36, 95% CI = 1.15-4.87) consisting of junior high school or below, being single (AOR = 2.27, 95% CI = 1.42-3.62), migrant background (AOR = 2.03, 95% CI = 1.29-3.20), and absence of any STI symptoms in the previous year (AOR = 1.66, 95% CI = 1.09-2.52). CONCLUSIONS: MG infection was prevalent among FSWs in the study areas. This pattern of infection suggests that an increasing attention should be paid to MG screening and treatment in this high risk population.

Path of Regional Economic Transformation and Upgrading Based on Recurrent Neural Network.

At present, the development of the regional economy is very rapid and widespread. However, due to increasingly prominent problems such as the low level of technological innovation and the unreasonable industrial structure, the economic growth rate has declined. Therefore, it is particularly important to use the circular economy network to study the transformation and upgrading of the regional economy. It clarifies the stakeholders in the process of transformation and upgrading of manufacturing enterprises. Its benefits in the network are given, and symptoms and mobilization methods and the obstacles and solutions to the development of mobilization among various subjects are drawn. In addition, it also emphasizes the equivalence between intelligent products and human subjects in this network. Because of the intelligence carried by products under the current background, diversified connotations and functions are becoming more and more abundant. The empirical results show that the pulling coefficients of residents' consumption level, the development of modern service industry, and urbanization rate to economic growth are 0.1812, 0.7165, and 0.1635, respectively, while the pulling coefficient of Gini coefficient to economic growth is -0.1785.

DEPTOR exacerbates bone-fat imbalance in osteoporosis by transcriptionally modulating BMSC differentiation.

Bone marrow-derived mesenchymal stem cells (BMSCs) tend to differentiate into adipocytes rather than osteoblasts in osteoporosis and other pathological conditions. Understanding the mechanisms underlying the adipo-osteogenic imbalance greatly contributes to the ability to induce specific MSC differentiation for clinical applications. This study aimed to explore whether DEP-domain containing mTOR-interacting protein (DEPTOR) regulated MSC fate and bone-fat switch, which was indicated to be a key player in bone homeostasis. We found that DEPTOR expression decreased during the osteogenesis of BMSCs but increased during adipogenesis and the shift of cell lineage commitment of BMSCs to adipocytes in mice with osteoporosis. DEPTOR facilitated adipogenic differentiation while preventing the osteogenic differentiation of BMSCs. Deptor ablation in BMSCs alleviated bone loss and reduced marrow fat accumulation in mice with osteoporosis. Mechanistically, DEPTOR binds transcriptional coactivator with a PDZ-binding motif (TAZ) and inhibits its transactivation properties, thereby repressing the transcriptional activity of RUNX2 and elevating gene transcription by peroxisome-proliferator-activated receptor-gamma. TAZ knockdown in BMSCs abolished the beneficial role of Deptor ablation in bone-fat balance in mice. Together, our data indicate that DEPTOR is a molecular rheostat that modulates BMSC differentiation and bone-fat balance, and may represent a potential therapeutic target for age-related bone loss.

HIV/STD pattern and its associated risk factors among male STD clinic attendees in China: a foci for HIV intervention.

BACKGROUND: Previous studies suggested a high prevalence of STDs including HIV among female sex workers and men who have sex with men in China, but little was known about the prevalence in male patients attending public STD clinics. The aim of this study was to investigate STD patterns and HIV prevalence among male STD clinic attendees in different areas in China and the associated risk factors. The feasibility of Provider-initiated HIV testing and counseling (PITC) was evaluated as well. METHODS: A cross-sectional study was conducted at 46 public STD clinics in 4 provinces in China. Between July 2009 and September 2009, a total of 3243 eligible subjects were invited to participate in an interview with a structured-questionnaire for collecting socio-demographic characteristics and sexual behavioral information. They also were asked to provide venous blood samples for serological determinations of HIV and syphilis infection, and first void urine specimens for detecting Chlamydia trachomatis and Neisseria gonorrhoeae infections, RESULTS: Out of the 3243 eligible patients, 2951(91%) men agreed to take part in the HIV and syphilis testing. The overall prevalence rate of HIV infection was 0.7% while the rates of syphilis, N. gonorrhoeae, C. trachomatis infections were 10.7%, 4.3% and 6.9%, respectively, with the highest syphilis and N. gonorrhoeae rates in Jiangsu Province. Patients from Guangxi province, homosexual/bisexual practices and intravenous drug use were significantly associated with HIV infection in multivariate logistic regression analyses. Provider-initiated HIV testing and counseling (PITC) was well accepted by attendees, with 91% of eligible attendees agreeing to undergo HIV testing and counseling. All HIV positive patients were properly managed accordingly. CONCLUSIONS: A modest prevalence of HIV infection and substantial prevalence of other STD infections were found among male patients attending public STD clinics in China. The findings further support the introduction of HIV and syphilis PITC strategy into this important setting.

METTL3 Contributes to Osteosarcoma Progression by Increasing DANCR mRNA Stability via m6A Modification.

Background: Osteosarcoma (OS) is the most prevalent bone cancer among children and adolescents, with relatively high mortality rates. RNA N6-methyladenosine (m6A) is the most common human mRNA modification with diverse functions in a variety of biological processes. Previous studies indicated that methyltransferase-like 3 (METTL3), the first methyltransferase to be identified, acted as an oncogene or tumor suppressor in multiple human cancers. However, its functions and underlying mechanisms in OS progression remain unclear; therefore, we explored these processes. Methods: We used real-time quantitative PCR (RT-qPCR) and Western blot assays to explore METTL3 expression in OS tumor tissues and five OS cell lines to assess its clinical significance. To further examine the functional role of METTL3 during OS progression, CCK-8 analyses, transwell assays, and xenograft model studies were conducted after silencing METTL3. Additionally, underlying mechanisms were also explored using RIP-seq and RIP-qPCR approaches. Results: METTL3 was upregulated in OS tumor tissues and cell lines and was associated with a worse prognosis. Moreover, METTL3 silencing suppressed OS cell proliferation, migration, and invasion. Also, in vivo METTL3 oncogenic functions were confirmed in the xenograft model. Comprehensive mechanistic analyses identified long non-coding RNA (lncRNA) DANCR as a potential target of METTL3, as indicated by reduced DANCR levels after METTL3 silencing. Also, lncRNA DANCR knockdown repressed OS cell proliferation, migration, and invasion. Furthermore, both METTL3 and lncRNA DANCR silencing significantly suppressed OS growth and metastasis. Finally, we hypothesized that METTL3 regulated DANCR expression via m6A modification-mediated DANCR mRNA stability. Conclusion: METTL3 contributes to OS progression by increasing DANCR mRNA stability via m6A modification, meaning that METTL3 may be a promising therapeutic target for OS treatment.

In vitro and in vivo evaluation of the pH-neutral bioactive glass as high performance bone grafts.

Osteogenic and angiogenic properties are two most valued factors for bone grafting materials. Biomedical materials with synergistic promotion effects on these two properties would be highly desirable. In this study, we showed that a recently developed pH-neutral bioactive glass (PSC) possessed such characteristics. Compared to two classical biomaterials, 45S5 bioactive glass and beta-tricalcium phosphate (ß-TCP), PSC markedly improved BMSCs' proliferation, migration and mineralization as well as their osteogenic and angiogenic differentiation. In vivo, PSC showed better performance on inducing bone regeneration than both 45S5 and ß-TCP, as featured by elevated bone mineral density (BMD) and new bone areas. PSC also significantly promoted new blood vessels formation compared with those in control groups. Furthermore, we revealed that PSC induced osteogenic and angiogenic differentiation of BMSCs through the PI3K/Akt/HIF-1α pathway, which had not been reported before. This synergistic effect of the PI3K/Akt/HIF-1α pathway on osteogenesis and angiogenic differentiation of BMSCs suggested that biomedical materials may promote new bone formation through multiple signal pathways, thus shedding light on the future development of materials with better performance.