A chest CT-based nomogram for predicting survival in acute myeloid leukemia.

BACKGROUND: The identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML). METHODS: 952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements. RESULTS: Three CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011). CONCLUSIONS: In summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

FAM83A has a pro-tumor function in ovarian cancer by affecting the Akt/Wnt/ß-catenin pathway.

Family with sequence similarity 83, member A (FAM83A) is a tumor-exclusive gene that has a vital role in numerous tumors. However, its role in tumorigenesis remains controversial. This work is dedicated to the study of the role of FAM83A in ovarian cancer. We observed elevated levels of FAM83A in ovarian cancer specimens and cells. Kaplan-Meier survival curves revealed that elevated FAM83A levels predicted a worse overall survival in ovarian cancer patients. The inhibition of FAM83A caused remarkable suppressive effects on the proliferation and invasion of ovarian cancer cells, and enhanced their chemosensitivity. On the contrary, the upregulation of FAM83A had opposite effects. Mechanistically, FAM83A had an effect on the Akt and Wnt/ß-catenin pathways in ovarian cancer cells. The repression of Akt could cancel the regulatory effect of FAM83A overexpression on the Wnt/ß-catenin pathway. Moreover, reactivation of the Wnt/ß-catenin pathway abolished FAM83A-inhibition-evoked antitumor effects. Additionally, FAM83A inhibition weakened the tumorigenic potential of ovarian cancer in vivo. Taken together, this work shows that FAM83A exerts a pro-tumor function in ovarian cancer by affecting the Akt/Wnt/ß-catenin pathway and proposes FAM83A as an effective and possible treatment target for ovarian cancer.

SUV39H1-DNMT3A-mediated epigenetic regulation of Tim-3 and galectin-9 in the cervical cancer.

BACKGROUND: Methylation of histone 3 at lysine 9 (H3K9) and DNA methylation are epigenetic marks correlated with genes silencing. The tumor microenvironment significantly influences therapeutic responses and clinical outcomes. The epigenetic-regulation mechanism of the costimulatory factors Tim-3 and galectin-9 in cervical cancer remains unknown. METHODS: The methylation status of HAVCR2 and LGALS9 were detected by MS-PCR in cervical cancer tissues and cell lines. The underlying molecular mechanism of SUV39H1-DNMT3A-Tim-3/galectin-9 regulation was elucidated using cervical cancer cell lines containing siRNA or/and over-expression system. Confirmation of the regulation of DNMT3A by SUV39H1 used ChIP-qPCR. RESULTS: SUV39H1 up-regulates H3K9me3 expression at the DNMT3A promoter region, which in turn induced expression of DNMT3A in cervical cancer. In addition, the mechanistic studies indicate that DNMT3A mediates the epigenetic modulation of the HAVCR2 and LGALS9 genes by directly binding to their promoter regions in vitro. Moreover, in an in vivo assay, the expression profile of SUV39H1 up-regulates the level of H3K9me3 at the DNMT3A promoter region was found to correlate with Tim-3 and galectin-9 cellular expression level. CONCLUSION: These results indicate that SUV39H1-DNMT3A is a crucial Tim-3 and galectin-9 regulatory axis in cervical cancer.

PACT cessation overcomes ovarian cancer cell chemoresistance to cisplatin by enhancing p53-mediated apoptotic pathway.

Ovarian cancer ranks as a lethal gynecological malignancy, and development of resistance to chemotherapy agents constitutes a major clinical challenge in ovarian carcinoma management. P53-associated cellular protein-testes derived (PACT) is recently proven to be expressed aberrantly in several cancers, and exerts a critical roles in cell proliferation, apoptosis and migration. Up to now, its function in chemoresistance of ovarian cancer remains poorly defined. In the present study, elevated expression of PACT was detected in cisplatin-resistant A2780/CP cells relative to cisplatin-sensitive A2780 cells. Moreover, exposure to cisplatin also increased PACT expression in A2780 cells. Functional assay confirmed that knockdown of PACT further aggravated the inhibitory effects of cisplatin on A2780 cell viability and enhanced cell apoptosis and caspase-3 activity in cisplatin-treated A2780 cells, indicating that PACT cessation elevates cell sensitivity to cisplatin in A2780 cells. Whilst, deletion of PACT affords little effects on cisplatin resistance in p53-defective SKOV3 cells. Mechanistic analysis corroborated that depression of PACT notably enhanced cisplatin-induced p53 expression, concomitant with the increases in p53-downstream Bax, p21 expression and decrease in Bcl-2 expression. Intriguingly, blocking the p53 pathway notably reversed PACT inhibition-increased cell sensitivity to cisplatin in A2780 cells by elevating cell viability and depressing cell apoptosis. Additionally, abrogation of p53 signaling also blunts PACT suppression-overcomed chemotherapy resistance to cisplatin in A2780/CP cells. Together, these findings confirm that targeting PACT may antagonize ovarian cancer cell resistance to cisplatin, supporting a promising therapeutic strategy to overcome the chemotherapy resistance in the treatment of ovarian cancer.

Evaluation of Risk Factors for Venous Thromboembolism in Patients Who Underwent Gynecological Surgery and Validation of a Fast-Rating Assessment Table.

BACKGROUND The aim of this study was to retrospectively analyze the risk factors for venous thromboembolism (VTE) in gynecological patients and verify the validity of a fast-rating assessment table. MATERIAL AND METHODS From October 2015 to October 2017, 53 patients complicated with VTE after gynecological operations were analyzed, and a total of 106 patients with 2 adjacent operations were selected as the control group. Factors such as age, body mass index (BMI), and tumor type were analyzed by univariate and multivariate analysis. A fast-rating assessment table of VTE risk factors was constructed. This fast-rating assessment table and the Caprini score table were used to compare the scores of all patients. RESULTS In the univariate analysis, there were significant differences in BMI, tumor type, operation duration, blood loss, blood transfusion, bed rest time, and thrombus-related history between the 2 groups. In the multiple factor analysis, age >60 years old, BMI >28 kg/m², malignant tumors, operation duration ≥3 hours, laparoscopic surgery and thrombus-related history were independent risk factors for VTE in patients. Both the fast-rating assessment table and the Caprini score table identified 90% of VTE patients as high-risk and very high-risk, and there was no significant difference between the tables. CONCLUSIONS Patients with older age, high BMI, malignant tumors, longer operation duration, laparoscopic surgery, or history of thrombosis may be more prone to VTE after gynecologic surgery. The fast-rating assessment table is easy to operate and has a high recognition level for VTE. It can be applied widely.

Magnetic Resonance Imaging (MRI) and Three-Dimensional Transvaginal Ultrasonography Scanning for Preoperative Assessment of High Risk in Women with Endometrial Cancer.

BACKGROUND To evaluate the diagnostic performance of MRI and 3D-TVS for assessment of deep myometrial invasion (MI), cervical involvement (CI), and Lymph node metastases (LNM) in endometrial cancer staging before surgery. MATERIAL AND METHODS From January 2016 to December 2017, we reviewed data from 314 women with endometrial cancer who underwent preoperative MRI and 3D-TVS before surgery. The diagnostic sensitivity, specificity, PPV, NPV, and accuracy in detecting MI, CI, and LNM were estimated based on ultimate pathology results. RESULTS The sensitivity, specificity, PPV, NPV, and accuracy of MRI in the diagnosis of MI were 89.19%, 88.97%, 67.35%, 97.99%, and 89.01%, respectively, and the indexes of 3D-TVS for MI were 86.36%, 91.07%, 79.17%, 94.44%, and 89.74%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of MRI for CI were 75% and 92.35%, 40.9%, 98.13%, and 91.2%, respectively. The indicators of 3D-TVS were 77.78%, 94.29%, 63.63%, 97.06%, and 92.4%, respectively. There were no significant differences in sensitivity, specificity, NPV, and accuracy between MRI and 3D-TVS in the diagnosis of MI and CI. For MI and CI, the sensitivity of combined MRI and 3D-TVS was higher than any other single method (P<0.05). For LNM, the sensitivity, specificity, PPV, NPV, and accuracy of MRI were 58.33%, 96.26%, 63.63%, 95.37%, and 92.43%, respectively. CONCLUSIONS 3D-TVS is equivalent to MRI in predicting MI and CI. Combined MRI and 3D-TVS can improve the assessment sensitivity, and they are useful in optimizing individualized surgical procedures. The sensitivity of MRI for LNM prediction needs to be improved.

Rate limiting factors for DNA transduction induced by weak electromagnetic field.

DNA transduction across aqueous solutions has been reported previously. In this study, we examined a few key factors affecting DNA transduction rate in an extremely low frequency electromagnetic field. These include: the chemical composition of the aqueous solutions, the type of experimental vessel, the dilution step, and the origin of the DNA fragments. The results indicate that partially introducing essential ingredients for DNA amplification (i.e. dNTPs and PCR buffer) to the aqueous solution enhanced the transduction rate greatly, and transduction vessels made of hydrophilic quartz yielded more favorable results than vessels made of hydrophobic plastic. In addition, performing a serial dilution to the transduction solution more than doubled the transduction rate compared to that without the dilution step. For the DNA fragments used in this study, there was one with a pathogenic origin and two with non-pathogenic origins. However, all three fragments achieved DNA transduction regardless of the difference in their origins. The experimental setup for eliminating the false positives caused by both biological and potentially physical contamination is also described.

Assessment of the effectiveness of HPV16/18 infection referred for colposcopy in cervical cancer screening in Northwest of China.

To evaluate the effectiveness of Human papillomavirus16/18 infection referral to colposcopy in cervical cancer screening for women aged 25 years and older in Chinese northwest region Shaan'xi province. A total of 2224 women were diagnosed with primary high-risk HPV infection by HPV-DNA genotyping technology during August 2014 to August 2015. A total of 1916 cases referred for colposcopy with histological evidence were enrolled, including 1124 women with HPV16/18 genotype and 792 with other High-risk human papillomavirus genotypes. A total of 1916 women aged 25 years and older with HR-HPV positive were referred to colposcopy. The distribution of HPV16, HPV18, and other HR-HPVs infection were 49.22%, 9.45%, and 41.33%, respectively. 71.56% had normal cervical histology, 7.05% had Cervical Intraepithelial Neoplasia1, 8.82% had CIN2, 7.25% had CIN3, and 5.32% had cervical cancer. The percentage of positivity of HPV16 and HPV18 was highly associated with the relative risk of cervical lesion. The sensitivity and specificity of HPV16/18 for detection of CIN2+ (CIN3+) was 82.68% (92.12%) and 47.87% (46.15%), respectively. The positive predictive value and negative predictive value of HPV16/18 for detection of CIN2+ (CIN3+) was 30.16% (19.75%) and 91.03% (97.60%), respectively. HPV16 and HVP18 are the most common genotypes in high grade cervical lesions in Shaan'xi province. Meanwhile, these two types play predominant roles in the progression of high grade cervical lesion. Primary HPV16/18 detection has high sensitivity and negative predictive value in cervical cancer screening and the strategy for women with HPV16 and HPV18 infection referral to colposcopy is efficient and feasible in northwestern region of China.

Prevalence of high-risk human papillomavirus infection among women in Shaanxi province of China: A hospital-based investigation.

This study aimed to investigate the characteristics of female high-risk human papillomavirus (HR-HPV) infection in Shaanxi province of China. A total of 14 111 women were enrolled for HPV genotyping test, and a cytology, and/or cervix biopsy were performed in partial women. Of these women, the HPV infection rate was 30.21%, and 26.73% were caused by HR-HPV. The most common HR-HPV genotypes were HPV-16, HPV-58, HPV-52, HPV-18, and HPV-31. The prevalence of HR-HPV among women older than 50 years was significantly higher than the other groups (P < 0.05). The main carcinogenic genotypes were HPV-16, HPV-18, HPV-58, HPV-52, and HPV-31. HPV-16 and HPV-18 combined caused 80.79% of cervical cancer cases. The infection with multiple HR-HPVs was not a risk factor for cervical lesions. In conclusion, HPV infection was common among women in Shaanxi province. Women older than 50 years were a high-risk group for HR-HPV infection and cervical cancer. HPV-16 and HPV-18 were the main carcinogenic genotypes in this region.

Negative immune factors might predominate local tumor immune status and promote carcinogenesis in cervical carcinoma.

BACKGROUND: The disequilibrium of local immune microenvironment is an essential element during tumorigenesis. METHOD: By conducting real-time polymerase chain reaction, we identified the mRNA level of immune factors, FoxP3 (forkhead box protein P3), CCL22/CCR4 (chemokine (C-C motif) ligand 22/CC chemokine receptor 4), OX40L/OX40 (tumor necrosis factor superfamily member 4/tumor necrosis factor receptor superfamily member 4) and Smad3 (SMAD family member 3) in neoplastic foci and its periphery tissues from 30 cases of squamous cervical carcinoma and 20 cases of normal cervix. RESULT: The FoxP3, CCL22 and CCR4 mRNA level in local immune microenvironment of normal cervix was lower than that in cervical cancer. While OX40L, OX40 and Smad3 mRNA level profile in normal cervix was higher than that in cervical cancer. Beyond individual effect, the pairwise positive correlations were demonstrated among the mRNA level of FoxP3, CCL22 and CCR4. The mRNA level of OX40 negatively correlated with CCL22, but positively correlated with Smad3. Moreover, the mRNA level of FoxP3 and CCL22 was increased while Smad3 was decreased in cervical tissue with HPV (human papilloma virus) infection. CONCLUSION: Our data yields insight into the roles of these immune factors in cervical carcinogenesis. It may therefore be that, in microenvironment of cervical squamous cell carcinoma, along with the context of HPV infection, negative immune regulators FoxP3, CCL22 and CCR4 might overwhelm positive immune factors OX40L, OX40 and Smad3, giving rise to an immunosuppressive status and promote the progression of cervical carcinogenesis. TRIAL REGISTRATION: Not applicable.

Expressions of Immune Negative Regulator FoxP3+Treg and PD-L1 Protein in the Immune Microenvironment of Cervical Lesion.

Objective To explore the expression patterns of immune negative regulator FoxP3+Treg and PD-L1 protein in cervical carcinoma and its precancerous lesions. Methods The expression patterns of FoxP3+Treg and PD-L1 protein in 45 cases of cervical lesions tissues of the cervix and 20 cases of normal cervix tissues by using immunohistochemistry (IHC). Results Compared with the normal cervix,the expressions of FoxP3+Treg (H=43.211,P=0.000) and PD-L1 protein (t=213.00,P=0.001) were significantly increased in cervical lesions. Compared with the low-grade squamous cell carcinoma,the invasiveness of FoxP3+Treg was increased in high-grade squamous cell carcinoma (H=28.307,P=0.000),along with increased expression of PD-L1 protein (t=239.000,P=0.028). The FoxP3+Treg expression was positively correlated with PD-L1 protein expression in abnormally differentiated cells (rs=0.364,P=0.003). Conclusion Along with the progression of cervical cancer,the FoxP3+Treg amount increases in the local microenvironment,along with enhanced PD-L1 protein expression in abnormally differentiated cells.

Immediate analgesic effect of needling acupoints (bilateral De Qi vs unilateral De Qi) on primary dysmenorrhea: a multi-center, randomized, controlled trail.

OBJECTIVE: To analyze the effect of needling acupoints (bilateral vs unilateral) with De Qi using data collected from 501 primary dysmenorrhea (PD) patients participating in multi-center, randomized, controlled trail. METHODS: De Qi was defined as at least one of the feelings in soreness, numbness, fullness or heaviness at the acupoints when stimulated with needles. The 501 patients were grouped in 3 groups in terms of De Qi or not De Qi in one side (unilateral) or both sides (bilateral) of the body: bilateral De Qi group, unilateral De Qi group, and non-De Qi group. The abdominal pains were measured using visual analog scale (VAS). RESULTS: In 501 patients, 472 acquired De Qi at unilateral acupoints, 24 De Qi at bilateral acupoint, and 5 had no De Qi at any acupoint. The data of non-De Qi group was excluded as the sample was less than 5% of that in the bilateral De Qi group. There was significant difference in the VAS before and after treatment between unilateral and bilateral De Qi group (P < 0.01). After stratified by acupoints, for the patients needled at Sanyinjiao (SP 6) and Xuanzhong (GB 39), VAS scores in the bilateral De Qi group were larger than those in the unilateral De Qi group (P < 0.05). CONCLUSION: Bilateral De Qi was possibly superior to unilateral De Qi in enhancing the immediate analgesic effect of needling the acupoints, but no statistical significance was observed on the patients of needling at non acupoint, which preliminarily suggested this immediate analgesic effect was perhaps along meridians.

Aberrant Expressions of Immune Factors Facilitate the Disequilibrium of Immune Status in Cervical Cancer.

Objective To explore the expressions and co-relationship of immune factors forkhead box p3 (FoxP3),chemokine (C-C motif) ligand 22 (CCL22),tumor necrosis factor receptor superfamily member 40(OX40),and SMAD family member 3 (Smad3) in cervical carcinoma and investigate their immunomodulatory roles in cervical carcinogenesis.Methods Totally 30 cases of cervical carcinoma with adjacent tissues and 20 cases of normal cervix were collected in this study. FoxP3,CCL22,OX40,and Smad3 mRNA expressions were detected by real-time polymerase chain reaction (RT-PCR). Results Compared to normal cervix,the expression levels of FoxP3 and CCL22 mRNA were elevated in neoplastic foci(P=0.000,P=0.002) and tumor periphery (P=0.048,P=0.040).The mRNAs increased modestly in high-grade squamous cell carcinoma focal(P=0.019,P=0.020) and periphery tissue (P=0.023,P=0.031) in comparison with low-grade squamous cell carcinoma. The expression levels of OX40 and Smad3 mRNA were significantly lower in neoplastic foci(P=0.000,P=0.015) than normal cervix. Compared to low-grade squamous cell carcinoma focal and periphery tissue,the mRNAs decreased moderately in high-grade squamous cell carcinoma(P=0.018,P=0.030; P=0.027,P=0.014). In both neoplastic foci and tumor periphery,the mRNA expression level of CCL22 was positively correlated with FoxP3 (r=0.353,P=0.000; r=0.307,P=0.000) but negatively correlated with OX40 (r=-0.288,P=0.031; r=-0.263,P=0.037),while OX40 was positively correlated with Smad3 (r=0.384,P=0.002;r=0.288,P=0.023). The mRNA expressions of FoxP3 and CCL22 were increased in foci and pericarcinous tissues (P=0.024,P=0.039; P=0.032,P=0.034) while Smad3 was decreased in neoplastic foci (P=0.017) in contrast to HPV negative corresponding group. Conclusion FoxP3 and CCL22 expressions increase while OX40 and Smad3 expression decrease at mRNA level in the microenvironment of cervical cancer,which may be associated with such immunological model that the immunosuppressive roles of FoxP3 and CCL22 enhance while the immunity-boosting roles of OX40 and Smad3 are impeded,contributing to the deterioration of immune disequilibrium in local site and cervical cancer carcinogenesis.

The carbon footprint of fast fashion consumption and mitigation strategies-a case study of jeans.

Fast fashion is driving the continued growth of the fashion industry's carbon emissions. Understanding how fast fashion consumption exacerbates carbon emissions is critical to guide mitigation strategies for the fashion industry. Taking jeans, a typical fast fashion product as an example, this study developed an LCA model to assess the carbon footprint of fast fashion consumption at global and national levels, and mitigation potentials of product service systems-related scenarios were then explored. Results show that the carbon footprint of fast fashion consumption is 2.50 kgCO2e/one wear jeans, 11 times higher than that of traditional fashion consumption. Jeans production and cross-broad transportation contributed 91 % of the carbon footprint of fast fashion consumption. Developed countries have a 53 % higher per capita carbon footprint of fast fashion consumption than developing countries. The second-hand trading model has the highest mitigation potential, reducing carbon emissions by 90 %. This study proposed an analytical framework for the carbon footprint of fast fashion consumption, which provides the basis for the environmental footprints of fast fashion products. Our findings provide insights into the carbon footprints of traditional and fast fashion consumption and strategies for the transition to circular fashion.

Characterization and Identification of NPK Stress in Rice Using Terrestrial Hyperspectral Images.

Due to nutrient stress, which is an important constraint to the development of the global agricultural sector, it is now vital to timely evaluate plant health. Remote sensing technology, especially hyperspectral imaging technology, has evolved from spectral response modes to pattern recognition and vegetation monitoring. This study established a hyperspectral library of 14 NPK (nitrogen, phosphorus, potassium) nutrient stress conditions in rice. The terrestrial hyperspectral camera (SPECIM-IQ) collected 420 rice stress images and extracted as well as analyzed representative spectral reflectance curves under 14 stress modes. The canopy spectral profile characteristics, vegetation index, and principal component analysis demonstrated the differences in rice under different nutrient stresses. A transformer-based deep learning network SHCFTT (SuperPCA-HybridSN-CBAM-Feature tokenization transformer) was established for identifying nutrient stress patterns from hyperspectral images while being compared with classic support vector machines, 1D-CNN (1D-Convolutional Neural Network), and 3D-CNN. The total accuracy of the SHCFTT model under different modeling strategies and different years ranged from 93.92% to 100%, indicating the positive effect of the proposed method on improving the accuracy of identifying nutrient stress in rice.

SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming.

Leukaemia stem cells (LSCs) in acute myeloid leukaemia present a considerable treatment challenge due to their resistance to chemotherapy and immunosurveillance. The connection between these properties in LSCs remains poorly understood. Here we demonstrate that inhibition of tyrosine phosphatase SHP-1 in LSCs increases their glycolysis and oxidative phosphorylation, enhancing their sensitivity to chemotherapy and vulnerability to immunosurveillance. Mechanistically, SHP-1 inhibition leads to the upregulation of phosphofructokinase platelet (PFKP) through the AKT-ß-catenin pathway. The increase in PFKP elevates energy metabolic activities and, as a consequence, enhances the sensitivity of LSCs to chemotherapeutic agents. Moreover, the upregulation of PFKP promotes MYC degradation and, consequently, reduces the immune evasion abilities of LSCs. Overall, our study demonstrates that targeting SHP-1 disrupts the metabolic balance in LSCs, thereby increasing their vulnerability to chemotherapy and immunosurveillance. This approach offers a promising strategy to overcome LSC resistance in acute myeloid leukaemia.

Super-enhancer-associated gene CAPG promotes AML progression.

Acute myeloid leukemia is the most common acute leukemia in adults, the barrier of refractory and drug resistance has yet to be conquered in the clinical. Abnormal gene expression and epigenetic changes play an important role in pathogenesis and treatment. A super-enhancer is an epigenetic modifier that promotes pro-tumor genes and drug resistance by activating oncogene transcription. Multi-omics integrative analysis identifies the super-enhancer-associated gene CAPG and its high expression level was correlated with poor prognosis in AML. CAPG is a cytoskeleton protein but has an unclear function in AML. Here we show the molecular function of CAPG in regulating NF-κB signaling pathway by proteomic and epigenomic analysis. Knockdown of Capg in the AML murine model resulted in exhausted AML cells and prolonged survival of AML mice. In conclusion, SEs-associated gene CAPG can contributes to AML progression through NF-κB.

LncRNA ABHD11-AS1 activates EGFR signaling to promote cervical cancer progression by preventing FUS-mediated degradation of ABHD11 mRNA.

Cervical cancer is one of the most common gynecological cancers with high metastasis, poor prognosis and conventional chemotherapy. The long non-coding RNA (lncRNA) ABHD11 antisense RNA 1 (ABHD11-AS1) plays a vital role in tumorigenesis and is involved in cell proliferation, differentiation, and apoptosis. Especially for cervical cancer, the functions and mechanisms of ABHD11-AS1 are still undetermined. In this study, we explored the role and underlying mechanism of ABHD11-AS1 in cervical cancer. We found that ABHD11-AS1 is highly expressed in cervical cancer tissue. The roles of ABHD11-AS1 and EGFR have investigated the loss of function analysis and cell movability in SiHa and Hela cells. Knockdown of ABHD11-AS1 and EGFR significantly inhibited the proliferation, migration, and invasion and promoted apoptosis of SiHa and Hela cells by up-regulating p21 and Bax and down-regulating cyclin D1, Bcl2, MMP9, and Vimentin. ABHD11-AS1 knockdown could decrease the expression of EGFR. In addition, ABHD11-AS1 could regulate the EGFR signaling pathway, including p-EGFR, p-AKT, and p-ERK. Spearman's correlation analysis and cell experiments demonstrated that ABHD11 was highly expressed in tumor tissue and partially offset the effect of shABHD11-AS1 on the proliferation, migration, and invasion of SiHa and Hela cells. Then, RNA pulldown was used to ascertain the mechanisms of ABHD11-AS1 and FUS. ABHD11-AS1 inhibited ABHD11 mRNA degradation by bounding to FUS. A subcutaneous xenograft of SiHa cells was established to investigate the effect of ABHD11-AS1 in tumor tissue. Knockdown of ABDH11-AS1 inhibited tumor growth and decreased the tumor volume. ABHD11-AS1 knockdown inhibited the expression of Ki67 and Vimentin and up-regulated the expression of Tunel. Our data indicated that ABHD11-AS1 promoted cervical cancer progression by activating EGFR signaling, preventing FUS-mediated degradation of ABHD11 mRNA. Our findings provide novel insights into the potential role of lncRNA in cervical cancer therapy.

PD-1 signalling defines and protects leukaemic stem cells from T cell receptor-induced cell death in T cell acute lymphoblastic leukaemia.

T cell acute lymphoblastic leukaemia (T-ALL) is an aggressive malignancy with poor prognosis, but a decisive marker and effective treatment for leukaemia stem cells (LSCs) remain unclear. Here, using lineage tracing, limiting dilution assays and in vivo live imaging approaches, we identify rare inhibitory receptor programmed cell death 1 (PD-1)-expressing cells that reside at the apex of leukaemia hierarchy for initiation and relapse in T-ALL. Ablation of PD-1-expressing cells, deletion of PD-1 in T-ALL cells or blockade of PD-1 or PD-1 ligand 1 significantly eradicated LSCs and suppressed disease progression. Combination therapy using PD-1 blockade and chemotherapy substantially extended the survival of mice engrafted with mouse or human T-ALL cells. Mechanistically, PD-1+ LSCs had high NOTCH1-MYC activity for disease initiation. Furthermore, PD-1 signalling maintained quiescence and protected LSCs against T cell receptor-signal-induced apoptosis. Overall, our data highlight the hierarchy of leukaemia by identifying PD-1+ LSCs and provide a therapeutic approach for the elimination of LSCs through PD-1 blockade in T-ALL.