Cloning and functional mechanism of the dwarf gene gba affecting stem elongation and cellulose biosynthesis in jute (Corchorus olitorius).

Plant height (PH) is an important factor affecting bast fiber yield in jute. Here, we report the mechanism of dwarfism in the 'Guangbaai' (gba) of jute. The mutant gba had shorter internode length and cell length compared to the standard cultivar 'TaiZi 4' (TZ4). Exogenous GA3 treatment indicated that gba is a GA-insensitive dwarf mutant. Quantitative trait locus (QTL) analysis of three PH-related traits via a high-density genetic linkage map according to re-seq showed that a total of 25 QTLs were identified, including 13 QTLs for PH, with phenotypic variation explained ranging from 2.42 to 74.16%. Notably, the functional mechanism of the candidate gene CoGID1a, the gibberellic acid receptor, of the major locus qPHIL5 was evaluated by transgenic analysis and virus-induced gene silencing. A dwarf phenotype-related single nucleotide mutation in CoGID1a was identified in gba, which was also unique to the dwarf phenotype of gba among 57 cultivars. Cogid1a was unable to interact with the growth-repressor DELLA even in the presence of highly accumulated gibberellins in gba. Differentially expressed genes between transcriptomes of gba and TZ4 after GA3 treatment indicated up-regulation of genes involved in gibberellin and cellulose synthesis in gba. Interestingly, it was found that up-regulation of CoMYB46, a key transcription factor in the secondary cell wall, by the highly accumulated gibberellins in gba promoted the expression of cellulose synthase genes CoCesA4 and CoCesA7. These findings provide valuable insights into fiber development affected by endogenous gibberellin accumulation in plants.

Predicting axillary metastasis in breast cancer using lymphatic contrast-enhanced ultrasound-guided fine-needle aspiration of one lymph node.

OBJECTIVES: Fine-needle aspiration (FNA) is a microinvasive method to diagnose lymph nodes. This study aims to determine the capability of lymphatic contrast-enhanced ultrasound (LCEUS)-guided FNA in predicting the axillary metastasis with the target of one lymph node (LN) in patients with breast cancer. METHODS: LCEUS was prospectively performed in 105 patients with breast cancer. The most suspicious LN was targeted based on the characters of LCEUS. FNA was performed in the LN, followed by localization using a guide wire. The detection of lymph cells and/or tumour cells was recognized as a puncture success. Cytologic diagnosis was compared with histologic diagnosis of wire-marked LN for diagnosing accuracy and compared with histologic diagnosis of axillary LNs for predicting accuracy. RESULTS: LCEUS-guided FNA was performed in all 105 female patients who underwent axillary dissection. The puncture success rates were 74.3%, 91.4%, and 97.1% for three sequential groups (P = .010). In diagnosing LN metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 89.7%, 100%, and 95.7%, respectively. In predicting axillary metastasis, the sensitivity, specificity, and accuracy values of LCEUS-guided FNA were 81.4%, 100%, and 91.3%, respectively. CONCLUSIONS: The microinvasive LCEUS-guided FNA of one lymph node can be an accurate method and may help predict axillary metastasis in patients with breast cancer. ADVANCES IN KNOWLEDGE: This study presented that LCEUS combined with FNA would be practical in clinic. The characters of LCEUS could indicate the suspicious LNs and promote the accuracy in predicting axillary metastasis.

Triptolide inhibits epithelial ovarian tumor growth by blocking the hedgehog/Gli pathway.

Epithelial ovarian cancer (EOC), the most predominant subtype of ovarian cancer (OC), involves poor prognosis and exhibits high aggression. Triptolide (TPL), like other Chinese herbs, has historically played a significant role in modern medicine. The screening system based on Gli-dependent luciferase reporter activity assessed the effects of over 800 natural medicinal materials on hedgehog (Hh) signaling pathway activity and discovered that TPL had an excellent inhibitory effect on Hh signaling pathway activity. However, the significance and mechanism of TPL involvement in regulating the Hh pathway have not been well explored. Thus, this work aimed to understand better how TPL affects the Hh pathway activity, which, in turn, influences the biological behavior of EOC. Our findings observed that Smo agonist SAG-induced EOC cell proliferation, migration, and invasion were drastically reversed by TPL in a concentration-dependent pattern. Further evidence suggested that TPL promotes the degradation of Gli1 and Gli2 to inhibit the activity of the Hh signaling pathway by relying on Gli1 and Gli2 ubiquitination. Our in vivo studies also confirmed that TPL could significantly inhibit the tumor growth of EOC. Taken together, our results revealed that one of the antitumor mechanisms of TPL was the targeted inhibition of the Hh/Gli pathway.

Enhancing the photodegradation of tetracycline in aquaculture wastewater via iron(III)-alginate: Degradation pathway transformation and toxicity reduction.

Tetracycline's (TC) incomplete self-photolysis by light irradiation generally produces toxic intermediate products, which posing serious harm to the aqueous environment. In order to diminish the environmental risks of TC self-photolysis, an iron(III)-alginate (Fe-SA) hydrogel assisted photocatalytic method was developed and the underlying mechanisms was also analyzed in this work. Under simulated sunlight, the photo-degradation efficiency of TC was 61.1% at pH 7.0 within 2 h. Importantly, four of the seven intermediate products that identified during the self-photolysis of TC were found toxic based on QSAR analysis. In contrast, the removal efficiency of TC could be improved to 87.4% by adding Fe-SA under the same conditions. Moreover, only two relatively weakly toxic intermediate products were detected after exposing to the Fe-SA photocatalytic system, indicating a significant reduction of the potential ecological risks caused by TC self-photolysis. Furthermore, the determination of reactive oxidation species (ROS) demonstrated that the addition of Fe-SA primarily facilitated the degradation of TC and the related toxic intermediate products through assisting the free radical (∙OH and ∙O2-) photocatalytic degradation pathway. Additionally, the photocatalytic application under actual sunlight conditions and the reusability experiments of Fe-SA further confirmed its effectiveness and low cost in removing TC. This study revealed the photodegradation mechanisms of TC from the perspective of the self-photolysis process, and also offering new insights into the removal of TC pollution in the environment.

Inhibit ALDH3A2 reduce ovarian cancer cells survival via elevating ferroptosis sensitivity.

Ovarian cancer (OC) is a malignant gynecologic tumor with high morbidity and mortality. As a newly discovered mode of programmed cell death, ferroptosis has been involved in various pathological processes of kinds of tumors in recent years. Aldehyde dehydrogenase 3 family member A2 (ALDH3A2) catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid. ALDH3A2 has been shown to be associated with ferroptosis in acute myeloid leukemia (AML), but the mechanism remains unclear. In this study, we analyzed the TCGA and GTEx databases and showed that high ALDH3A2 expression predicted poor prognosis in ovarian cancer. Further studies found that knockout or overexpression of ALDH3A2 correspondingly increased or attenuated the ferroptosis sensitivity of ovarian cancer cells. And sequencing revealed that ALDH3A2 knockout led to the activation of lipid metabolic, GSH metabolic, phospholipid metabolic, and aldehyde metabolic pathways, suggesting that ALDH3A2 induced changes in the sensitivity of ovarian cancer cells to ferroptosis by affecting these metabolic processes. Our results provide a new promising therapeutic strategy for the treatment of OC.

The efficacy and influence factors analysis of Mifepristone combined with estrogen-progesterone in the treatment of incomplete abortion.

To analyze the efficacy and influencing factors of Mifepristone combined with estrogen-progesterone sequential therapy (Femoston) in the treatment of incomplete abortion. This retrospective cohort study included 93 patients with incomplete abortion. All patients took 50 mg of Mifepristone 2 times a day for 5 days and then took Femoston once a day (starting with estradiol tablets/2 mg) for 28 days. Without any indication of intrauterine residue by ultrasonic examination was judged to be effective. According to statistical analysis, this study calculated the effective rate and analyzed its influencing factors. A 2-sided value of P < .05 was considered statistically significant. The total response rate of the treatment regimen was 86.67%. body mass index was a significant influencing factor for treatment outcome (OR 0.818, 95% confidence interval 0.668-0.991, P = .041). For patients with incomplete abortion, Mifepristone combined with estrogen-progesterone sequential therapy has a remarkable therapeutic effect. Patients with a lower body mass index may respond much more significantly to this treatment regimen.

A comprehensive analysis of PANoptosome to prognosis and immunotherapy response in pan-cancer.

PANoptosis, a programmed cell death, shares key characteristics of apoptosis, pyroptosis, and necroptosis. Accumulating evidence suggests that PANoptosis plays a crucial role in tumorigenesis. However, the respective regulation mechanisms in cancer are so far unclear. Using various bioinformatic approaches, we comprehensively analyzed the expression patterns, genetic alterations, prognostic value, and immunological role of PANoptosis genes in pan-cancer. Expression of the PANoptosis gene, PYCARD, was validated based on the Human Protein Atlas database and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). We found that PANoptosis genes were aberrantly expressed in most cancer types, which was consistent with the validation of PYCARD expression. Concurrently, PANoptosis genes and PANoptosis scores were significantly associated with patient survival in 21 and 14 cancer types, respectively. Pathway analysis showed that PANoptosis score was positively correlated with pathways linked to immune and inflammatory responses in pan-cancer, such as IL6-JAK-STAT3 signaling, the interferon-gamma response, and IL2-STAT5 signaling. In addition, the PANoptosis score was significantly correlated with the tumor microenvironment, the infiltration levels of most immune cells (i.e.NK cells, CD8+ T cells, CD4+ T cells, DC cells), and immune-related genes. Furthermore, it was a predictive indicator of immunotherapy response in patients with tumors. These insights substantially improve our understanding of PANoptosis components in cancers and may inspire the discovery of novel prognostic and immunotherapy response biomarkers.

Correlation Analysis and Application of Respiratory and Lung Diseases in Pediatrics of Traditional Chinese Medicine Based on Factor Analysis Method.

Many scholars have studied the influencing factors of children's lung infection, whether it is the region or the environment, or the living air quality of the mother during pregnancy. Western medicine is the most frequently used medicine, but Chinese medicine has more remarkable characteristics in treating children's lung diseases. For viral invasive diseases, people often use antibiotics to treat them. Children's lung conditions are too fragile, and taking antibiotics will lead to the damage of Staphylococcus in the lungs, resulting in pulmonary respiratory insufficiency. Although the conditioning time of traditional Chinese medicine is longer than that of western medicine, traditional Chinese medicine will not cause secondary damage to the lungs. In this paper, we introduce factor analysis and principal component analysis and compare the performance of the three analysis methods by using data such as cure rate, improvement rate, mortality rate, and drug taking frequency as evaluation indexes. In the model comparison, the accuracy rate of factor analysis method is over 97%, while the error rate is below 5%. Compared with the other two analysis methods, this method has a better application effect. Finally, we compare the comprehensive scores of eigenvalues of the three analysis methods. From 2016 to 2021, the comprehensive scores of factor analysis gradually increased.

Identification of an Epithelial-Mesenchymal Transition-Related Long Non-coding RNA Prognostic Signature to Determine the Prognosis and Drug Treatment of Hepatocellular Carcinoma Patients.

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. Epithelial-mesenchymal transition (EMT) is crucial for cancer progression and metastasis. Thus, we aimed to construct an EMT-related lncRNA signature for predicting the prognosis of HCC patients. Methods: Cox regression analysis and LASSO regression method were used to build an EMT-related lncRNAs risk signature based on TCGA database. Kaplan-Meier survival analysis was conducted to compare the overall survival (OS) in different risk groups. ROC curves and Cox proportional-hazards analysis were performed to evaluate the performance of the risk signature. RT-qPCR was conducted in HCC cell lines and tissue samples to detect the expression of some lncRNAs in this risk model. Furthermore, a nomogram involving the risk score and clinicopathological features was built and validated with calibration curves and ROC curves. In addition, we explored the association between risk signature and tumor immunity, somatic mutations status, and drugs sensitivity. Results: Twelve EMT-related lncRNAs were obtained to construct the prognostic risk signature for patients with HCC. The Kaplan-Meier curve analysis revealed that patients in the high-risk group had worse overall survival (OS) than those in low-risk group. ROC curves and Cox regression analysis suggested the risk signature could predict HCC survival exactly and independently. The prognostic value of the risk model was confirmed in the testing and entire groups. We also found AC099850.3 and AC092171.2 were highly expressed in HCC cells and HCC tissues. The nomogram could accurately predict survival probability of HCC patients. Gene set enrichment analysis (GSEA) and gene ontology (GO) analysis showed that cancer-related pathways and cell division activity were enriched in high-risk group. The SNPs showed that the prevalence of TP53 mutations was significantly different between high- and low-risk groups; the TP53 mutations and the high TMB were both associated with a worse prognosis in patients with HCC. We also observed widely associations between risk signature and drugs sensitivity in HCC. Conclusion: A novel EMT-related lncRNAs risk signature, including 12 lncRNAs, was established and identified in patients with HCC, which can accurately predict the prognosis of HCC patients and may be used to guide individualized treatment in the clinical practice.

Evaluation of whole axillary status with lymphatic contrast-enhanced ultrasound in patients with breast cancer.

OBJECTIVES: This study aims to evaluate the whole axillary status of patients with breast cancer by lymphatic contrast-enhanced ultrasound (LCEUS). METHODS: LCEUS was applied for 169 patients with suspected breast cancer. Abnormal patterns in lymphatic channels, sentinel lymph nodes (SLNs), and non-enhanced but abnormal lymph nodes were investigated. The signs of distorted, attenuated, netted, or interrupted lymphatic channels, defective-filling or no-filling SLNs, and the appearance of non-enhanced but abnormal lymph nodes were designated as features of axillary metastasis. A positive outcome was given when any of the abnormal patterns was found in the LCEUS. The diagnostic efficiencies were calculated to differentiate the axillary lymphatic status using LCEUS for the whole axilla, compared with conventional ultrasound (US) and LCEUS for SLNs. RESULTS: The LCEUS procedure was successfully performed for 157 breast cancer patients with axillary dissection. Compared to normal axillae, abnormal patterns had a significantly higher frequency in metastatic axillae (p = 0.000). Using conventional US to evaluate the whole axillae, the diagnostic sensitivity, specificity, and accuracy were 69.1%, 71.9%, and 70.7%, respectively. When LCEUS was used for SLN evaluation to predict the whole axilla, the diagnostic sensitivity, specificity, and accuracy were 66.2%, 89.9%, and 79.6%, respectively. When LCEUS was used as the whole axillary evaluation method, the diagnostic sensitivity, specificity, and accuracy were 76.5%, 86.5%, and 82.2%, respectively. CONCLUSION: LCEUS can be an accurate method to observe the whole axillae in breast cancer patients. Lymphatic channels, SLNs, and non-enhanced but abnormal lymph nodes constitute the LCEUS for whole axillary evaluation. KEY POINTS: • LCEUS can be an accurate method to observe the whole axillae in breast cancer patients. • Three aspects in the LCEUS for whole axillary evaluation are the lymphatic channels, sentinel lymph nodes (SLNs), and non-enhanced but abnormal lymph nodes. • Signs of distorted, attenuated, netted, or interrupted lymphatic channels, defective-filling or no-filling SLNs, and the appearance of non-enhanced but abnormal lymph nodes were considered as features of axillary metastasis.

Comparison of lymphatic contrast-enhanced ultrasound and intravenous contrast-enhanced ultrasound in the preoperative diagnosis of axillary sentinel lymph node metastasis in patients with breast cancer.

OBJECTIVES: This study aimed to compare diagnostic efficiency for axillary sentinel lymph node (SLN) metastasis between lymphatic contrast-enhanced ultrasound (LCEUS) and intravenous contrast-enhanced ultrasound (ICEUS) in patients with breast cancer. We also examined whether adding ICEUS to LCEUS could improve the diagnostic accuracy of LCEUS. METHODS: Sixty-nine patients with breast cancer were recruited preoperatively. All patients underwent LCEUS followed by ICEUS, and the enhancement pattern of one SLN was analysed for each patient. The targeted SLN was marked with wire and excised during surgery. The imaging diagnosis was compared with the histopathological result. Diagnostic efficiency was compared among LCEUS, ICEUS, and the combination of LCEUS and ICEUS. RESULTS: The sensitivity values for LCEUS, ICEUS, and the combination of LCEUS and ICEUS were 86.2%, 82.6% and 93.1%, respectively. Specificity values for the three methods were 95.0%, 92.5% and 87.5%, respectively. Accuracy values for the three methods were 91.3%, 88.4% and 89.9%, respectively. The area under the receiver operating characteristic (ROC) curve for LCEUS was 0.906, and there was no significant difference among LCEUS, ICEUS, and the combination of LCEUS and ICEUS (p = 0.752). CONCLUSIONS: LCEUS may represent an accurate method for predicting SLN metastasis preoperatively. Our findings suggest that adding ICEUS to LCEUS for SLN evaluation in patients with breast cancer is unnecessary. ADVANCES IN KNOWLEDGE: This is the first study in which both LCEUS and ICEUS were performed for the same lymph node and the first to compare the diagnostic efficiency of LCEUS, ICEUS, and the combination of LCEUS + ICEUS.

Efficacy of Acupuncture Combined with Rehabilitation Training for Intensive Care Unit-Acquired Muscle Weakness: A Protocol for a Randomized, Sham-Procedure-Controlled Clinical Trial.

To evaluate the efficacy of acupuncture combined with rehabilitation training in patients with intensive care unit (ICU)-acquired muscle weakness (ICUAW), a single-blinded, randomized, sham-controlled clinical trial is designed for execution. In total, 56 participants with ICUAW will be randomly assigned to the treatment and control groups with 28 participants in each group. The participants will be treated with acupunctures or sham procedures at LI15, LI11, ST36, GB34, and ST31, 5 times per week for a total of 20 sessions in 4 weeks while they will receive rehabilitation training. Patients will be followed up every month for 3 months after treatment. The primary outcomes include changes in quadriceps femoris muscle area, thickness, vastus intermediate muscle thickness, subcutaneous tissue thickness, and ultrasonic intensities of the rectus femoris. The secondary outcomes consist of the modified Barthel index score and the Medical Research Council total score. Participants' mechanical ventilation, the rate of detachment at the second week, the 28-day survival rate, and the occurrence of adverse reactions will be measured, and any side effects will be reported and recorded. Patient outcomes between the treatment and control groups will be compared and statistically tested. We anticipate that the therapeutic regimen of acupuncture combined with rehabilitation training would be more effective than the rehabilitation training alone for the treatment of the ICUAW. The findings of this study could help develop a better strategy for the treatment of the ICUAW disease and explore a clinical application of an acupuncture technique. Trial registration: Chinese Clinical Trial Register ChiCTR2000038779. Registered 30 September, 2020, https://www.chictr.org.cn/showproj.aspx?proj=62284.

Family Sibling Effect and Executives' Corporate Social Behavior.

Corporate social responsibility is an important business strategy for enterprises. Scholars have conducted much beneficial research on the relationship of executives' recognitive traits and firms' CSR behavior, but rarely focus on the impact of executives' early recognitive traits derived from family sibling interaction. This paper takes Chinese A-shared private listed companies from 2014 to 2017 as the research samples to investigate the effect of the number of executives' siblings on the early family sibling and corporate social responsibility behavior. We further study the moderating effect of birth order and gender composition in siblings on this relationship. The results show that there is an inversed U-shaped relationship between the number of executives' siblings and corporate social responsibility behavior. Further research shows that the relationship between the number of executives' siblings and CSR behavior is strengthened when an executive is first-born or has female sibling(s).

Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma.

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the "limma" package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

A meta-analysis of the efficacy and safety of adjuvant sorafenib for hepatocellular carcinoma after resection.

BACKGROUND: Sorafenib was reported as a useful adjuvant treatment in patients with hepatocellular carcinoma who underwent surgical resection. However, its therapeutic value remains controversial. This meta-analysis examined the available data regarding the efficacy and safety of sorafenib in patients with hepatocellular carcinoma after radical surgery. METHODS: The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered in advance with PROSPERO (CRD42021233868). We searched PubMed, Embase, Cochrane Library, and Web of Science to identify eligible studies. Overall survival, recurrence-free survival, and recurrence rates were analyzed, and adverse events were reviewed. Hazard ratios or pooled risk ratios with 95% CIs were collected and analyzed using STATA version 12.0 in a fixed-effects or random-effects meta-analysis model. RESULTS: In total, 2655 patients from 13 studies were ultimately included in this meta-analysis. The combined results illustrated that sorafenib was associated with better overall survival than the control (hazard ratio = 0.71, 95% CI = 0.59-0.86; P < 0.001). Similarly, the drug also improved recurrence-free survival (hazard ratio = 0.68, 95% CI = 0.54-0.86, P = 0.001). Combined data revealed that patients treated with sorafenib after resection had a lower recurrence rate (pooled risk ratio = 0.78, 95% CI = 0.68-0.90, P < 0.001). The primary adverse events were hand-foot skin reaction, fatigue, and diarrhea of mild-to-moderate severity, whereas grade 4 adverse events were rare (< 1%). CONCLUSIONS: This meta-analysis demonstrated that adjuvant sorafenib therapy after resection in patients with hepatocellular carcinoma could prolong overall survival and recurrence-free survival and reduce recurrence rates without intolerable side effects. However, more evidence is needed before reaching a definitive conclusion.

PPARγ induces the paroxysm of endometriosis by regulating the transcription of MAT2A gene.

OBJECTIVE: To investigate the molecular mechanism of PPARγ impacting the paroxysm of endometriosis. METHODS: Immunohistochemistry, qRT-PCR and Western Blot were used to determine the expression level of PPARγ and MAT2A in Eu, Ec and normal endometrial tissue (control). ESC and NSC were separately isolated. PPARγ was silenced in NSC and was up-regulated in ESC. Rosiglitazone (RSG) were used to incubate with ESC. Proliferation, apoptosis, invasion, and ultrastructure of cells were evaluated in vitro. The combination between PPARγ and the promoters of MAT2A was detected by dual-luciferase reporter assay. RESULTS: MAT2A was up-regulated and PPARγ was down-regulated in Eu and Ec. The cell viability and the ability of migration and invasion declined greatly after up-regulating the expression of PPARγ or treating with RSG in ESC. Meanwhile, the expression level of MAT2A was significantly inhibited. Plenty of vacuoles and classical morphological changes of apoptotic cells were observed in the ESC with PPARγ over-expressed. The cell viability and the ability of migration and invasion of NSC with PPARγ silenced were promoted greatly. Meanwhile, the expression level of MAT2A was significantly up-regulated. CONCLUSION: The paroxysm and development of endometriosis were impacted by over-expressing PPARγ or introducing of RSG by inhibiting the transcription of MAT2A.

Identification of Novel Tumor Microenvironment-Related Long Noncoding RNAs to Determine the Prognosis and Response to Immunotherapy of Hepatocellular Carcinoma Patients.

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. The tumor microenvironment (TME) plays a vital role in HCC progression. Thus, this research was designed to analyze the correlation between the TME and the prognosis of HCC patients and to construct a TME-related long noncoding RNA (lncRNA) signature to determine HCC patients' prognosis and response to immunotherapy. Methods: We assessed the stromal-immune-estimate scores within the HCC microenvironment using the ESTIMATE (Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data) algorithm based on The Cancer Genome Atlas database, and their associations with survival and clinicopathological parameters were also analyzed. Thereafter, differentially expressed lncRNAs were filtered out according to the immune and stromal scores. Cox regression analysis was performed to build a TME-related lncRNA risk signature. Kaplan-Meier analysis was used to explore the prognostic value of the risk signature. Furthermore, we explored the biological functions and immune microenvironment features in the high- and low-risk groups. Lastly, we probed the association of the risk model with treatment responses to immune checkpoint inhibitors (ICIs) in HCC. Results: The stromal, immune, and estimate scores were obtained utilizing the ESTIMATE algorithm for patients with HCC. Kaplan-Meier analysis showed that high scores were significantly correlated with better prognosis in HCC patients. Six TME-related lncRNAs were screened to construct the prognostic model. The Kaplan-Meier curves suggested that HCC patients with low risk had better prognosis than those with high risk. Receiver operating characteristic (ROC) curve and Cox regression analyses indicated that the risk model could predict HCC survival exactly and independently. Functional enrichment analysis revealed that some tumor- and immune-related pathways were activated in the high-risk group. We also revealed that some immune cells, which were important in enhancing immune responses toward cancer, were significantly increased in the low-risk group. In addition, there was a close correlation between ICIs and the risk signature, which can be used to predict the treatment responses of HCC patients. Conclusion: We analyzed the influence of the stromal, immune, and estimate scores on the prognosis of HCC patients. A novel TME-related lncRNA risk model was established, which could be effectively applied as an independent prognostic biomarker and predictor of ICIs for HCC patients.

Hedgehog-Gli2 Signaling Promotes Chemoresistance in Ovarian Cancer Cells by Regulating MDR1.

BACKGROUND: Cisplatin (DDP) resistance remains a key challenge in improving the clinical outcome of patients with ovarian cancer (OC). Gli2 overexpression can lead to DDP resistance in OC cells, but the specific underlying regulatory mechanism remains unclear. The membrane transporter encoding gene MDR1 positively regulates chemotherapy resistance in various cancer types. We evaluated MDR1 as a potential Gli2 downstream target and the contribution of the Gli2/MDR1 axis in promoting DDP resistance in OC cells. METHODS: To generate drug-resistant SKOV3/DDP cells, SKOV3 cells were grown for six months under continuous induction wherein the DDP concentration was steadily increased. Gli2 expression in OC cells with varying DDP sensitivities was detected using western blot. Cell counting kit-8 assays were used to assess the DDP sensitivity of SKOV3, SKOV3/DDP, A2780, and A2780/DDP cells and reversal of DDP resistance in SKOV3/DDP and A2780/DDP cells. Cell proliferation was analyzed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. The transcriptional regulation of MDR1 by Gli2 was determined using luciferase reporter assays. Finally, xenograft OC tumors were generated in nude mice, which were then treated with intraperitoneal DDP or phosphate-buffered saline (PBS) injections to investigate if Gli2 affected DDP resistance in OC in vivo. RESULTS: DDP-resistant SKOV3/DDP and A2780/DDP cells showed higher expression of Gli2 and MDR1 as compared with that in DDP-sensitive OC cells. Gli2 knockdown in SKOV3/DDP cells significantly reduced MDR1 expression, whereas it increased DNA damage, thereby sensitizing OC cells to DDP. Similar results were obtained after targeting Gli2 expression with the Gli-antagonist 61 inhibitor (GANT61) in SKOV3/DDP and A2780/DDP cells. In cells stably overexpressing Gli2, treatment with gradient concentrations of verapamil, an MDR1 inhibitor, significantly inhibited MDR1 expression. Our findings indicate that downregulation of MDR1 expression may reverse OC cell resistance to DDP. Moreover, dual-luciferase reporter gene assays confirmed that MDR1 is a direct downstream target of Gli2, with Gli2 positively regulating MDR1 expression. Finally, subcutaneous xenotransplantation in nude mice demonstrated that Gli2 plays a key role in regulating OC drug resistance. CONCLUSIONS: We identified a mechanism by which Hedgehog-Gli signaling regulates OC chemoresistance by modulating MDR1 expression. Hence, Gli2 and MDR1 are potential biomarkers and therapeutic targets in patients with chemoresistant OC.

Rosiglitazone affects the progression of surgically­induced endometriosis in a rat model.

Endometriosis is closely associated with inflammatory reactions and angiogenesis. Whether PPARγ is a target for the treatment of endometriosis remains unknown. The present study was designed to investigate the impact of a PPARγ agonist (rosiglitazone, RSG) on endometriosis in a rat model and to identify the underlying mechanism. The endometriosis model was established in rats. The pathological state of the endometrium was examined using hematoxylin­eosin staining. The microstructures of interest were visualized using electron microscopy. Western blot analysis and reverse transcription­quantitative polymerase chain reaction were used to detect PPARγ and MAT2A expression. VEGF and caspase­3 expression were investigated using immunohistochemistry. Pathological analysis revealed transparent and red nodules in the model group, and that vasoganglions were present all over the nodules. Endometrial epithelial hyperplasia was observed in the model group, and the shape was columnar. Increased interstitial cell numbers, with compact structure and abundant blood supply, were detected in the model group. Compared with the model group, incomplete epithelial structures with sparse interstitial cells and loose structure were observed in the pathological images from RSG treatment groups. Numerous inflammatory cells and poor blood supply were observed in the endometrial tissues, and the gland was filled mostly with vacuolar cells. Electron microscopy revealed that the tissue structure was integrated. Many vacuoles were formed within the endometrial tissue and the classical morphological changes of apoptotic cells were observed in RSG­treated groups. Caspase­3 and PPARγ expression increased and expression of VEGF and MAT2A decreased in RSG­treated groups. Taken together, these results revealed that RSG impacts the development and progression of endometriosis likely by inhibiting angiogenesis and inducing apoptosis.

Long non-coding RNA MINCR aggravates colon cancer via regulating miR-708-5p-mediated Wnt/ß-catenin pathway.

BACKGROUND: Increasing evidence has found that the dysregulation of long non-coding RNAs (lncRNAs) may be important indicators in tumorigenesis. MYC-induced long non-coding RNA (MINCR) has been found to be related with some cancers, such as non-small cell lung cancer and gallbladder cancer. Besides, MINCR has potentially prognostic value for colon cancer (CC) patients' prognosis, yet its function and molecular mechanism in CC are not explored. METHODS: qRT-PCR evaluated gene expression, and western blot detected protein level. In vitro and in vivo experiments were adopted to understand the biological role of MINCR in CC. TOP/FOP Flash assay was performed to measure the activity of Wnt/ß-catenin pathway. RNA pull down, luciferase reporter and RIP assays were utilized to analyze the relationship among genes. Immunohistochemistry and HE staining techniques were utilized to evaluate Ki67 staining in xenografts. RESULTS: MINCR was up-regulated in CC cells. Knockdown of MINCR suppressed cell proliferation and migration. MINCR could up-regulate CTNNB1 via sequestering miR-708-5p, resulting in activated Wnt/ß-catenin pathway. The addition of LiCl treatment, miR-708-5p inhibitor or pcDNA3.1/CTNNB1 abolished the inhibitory impacts induced by MINCR silence in CC progression. CONCLUSION: MINCR sponges miR-708-5p to up-regulate CTNNB1 and activate Wnt/ß-catenin pathway, thus promoting the development CC. Targeting MINCR might shed new light on the therapeutic strategies of CC.