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Abstract Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

Abstract Background Some biomarkers collected from routine laboratory tests have shown important value in cancer prognosis. The study aimed to evaluate the prognostic significance of routine laboratory biomarkers in patients with endometrial cancer (EC) and to develop credible prognostic nomogram models for clinical application. Methods A total of 727 patients were randomly divided into a training set and a validation set. Cox proportional hazards models were used to evaluate each biomarker’s prognostic value, and independent prognostic factors were used to generate overall survival (OS) and progression-free survival (PFS) nomgrams. The efficacy of the nomograms were evaluated by Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration curves, X-tile analysis and Kaplan‒Meier curves. Results Ten significant biomarkers in multivariate Cox analysis were integrated to develop OS and PFS nomograms. The C-indices of the OS- nomogram in the training and validation sets were 0.885 (95% confidence interval (CI), 0.810–0.960) and 0.850 (95% CI, 0.761–0.939), respectively; those of the PFS- nomogram in the training and validation sets were 0.903 (95% CI, 0.866–0.940) and 0.825 (95% CI, 0.711–0.939), respectively. ROC, DCA and calibration curves showed better clinical application value for the nomograms incorporating routine laboratory biomarkers. X-tile analysis and Kaplan‒Meier curves showed that the nomograms were stable and credible in evaluating patients at different risks. Conclusions Nomogram models incorporating routine laboratory biomarkers, including NLR, MLR, fibrinogen, albumin and AB blood type, were demonstrated to be simple, reliable and favourable in predicting the outcomes of patients with EC.

The distribution line is widely distributed and the span of pole-towers is small. However, the existing lightning positioning system has limited positioning accuracy, and the lightning strike coordinates it locates have certain deviations for the distribution network. The lightning hazard risk divided by lightning density is not sufficient to support the differentiated lightning protection transformation of the distribution network. The environment of the underlying surface where the pole-tower is located has a significant impact on lightning activity, so this paper combines terrain, climate, lightning current characteristics, and historical lightning trip data to finely evaluate the lightning risk level in the distribution line pole-tower area. This paper provides a detailed analysis of the relationship between different underlying surface environments and lightning current characteristics and utilizes the entropy weight method to construct a comprehensive lightning disaster risk index, then evaluates the risk level of lightning disaster in different regions, and corrects it through lightning fault data. Overlaying the risk level of the area and the distribution map of the pole-tower foundation coordinates, it will obtain the distribution of lightning hazard-pregnant risk at the pole-tower area, which would contribute to guiding the differentiated lightning protection transformation of the line. Compared to traditional unified lightning protection renovation methods, differentiated lightning protection methods that integrate factors such as pole-tower structure, wire type, and lightning risk level can achieve significant lightning protection effects at a lower economic cost. Taking Nanchang City as an example, risk assessment and lightning protection renovation were conducted on 21 distribution lines. The average number of lightning trips per year is 55 before the renovation, but it is only 4 after the renovation, which the number of lightning trips significantly reduce. This verifies the effectiveness of using lightning hazard-pregnant assessment results to guide differentiated lightning protection methods.

In this work, we proposed a triboelectric nanogenerator (TENG) based on cellulose nanocrystal (CNC)/gelatin composite film (CG-TENG) to monitor the posture and movements of athletes during jumping training. The triboelectric layers comprise a polytetrafluoroethylene film (which carries a negative charge) and a CNC/gelatin composite film (manifesting a positive charge). The CNC is derived from recycled wasted boxes using the traditional sulfuric acid hydrolysis method and is incorporated into the gelatin film as a nanoscale additive. By utilizing an external load resistance measuring 20 MΩ, it is possible to attain an all-time high instantaneous power of 583 µW. The electrical output of the CG-TENG demonstrates notable stability and endurance, as it maintains a consistent pattern during a duration of more than 30 000 cycles. By capitalizing on sustainable and green materials, the CG-TENG paves the way for innovative sports monitoring solutions, amplifying the potential for human physiological signal tracking.

Abstract Tumor stem cells (TSCs) are thought to contribute to the progression and maintenance of cancer. Previous studies have suggested that plasmacytoma variant translocation 1 (PVT1) has a tumor-promoting effect on endometrial cancer; however, its mechanism of action in endometrial cancer stem cells (ECSCs) is unknown. Here, we found that PVT1 was highly expressed in endometrial cancers and ECSCs, correlated with poor patient prognosis, promoted the malignant behavior and the stemness of endometrial cancer cells (ECCs) and ECSCs. In contrast, miR-136, which was lowly expressed in endometrial cancer and ECSCs, had the opposite effect, and knockdown miR-136 inhibited the anticancer effects of down-regulated PVT1. PVT1 affected miR-136 specifically binding the 3’ UTR region of Sox2 by competitively “sponging” miR-136, thus positively saving Sox2. Sox2 promoted the malignant behavior and the stemness of ECCs and ECSCs, and overexpression Sox2 inhibited the anticancer effects of up-regulated miR-136. Sox2 can act as a transcription factor to positively regulate Up-frameshift protein 1 (UPF1) expression, thereby exerting a tumor-promoting effect on endometrial cancer. In nude mice, simultaneously downregulating PVT1 and upregulating miR-136 exerted the strongest antitumor effect. We demonstrate that the PVT1/miR-136/Sox2/UPF1 axis plays an important role in the progression and maintenance of endometrial cancer. The results suggest a novel target for endometrial cancer therapies.

Flat panel displays are electronic displays that are thin and lightweight, making them ideal for use in a wide range of applications, from televisions and computer monitors to mobile devices and digital signage. The Thin-Film Transistor (TFT) layer is responsible for controlling the amount of light that passes through each pixel and is located behind the liquid crystal layer, enabling precise image control and high-quality display. As one of the important parameters to evaluate the display performance, the faster response time provides more frames in a second, which benefits many high-end applications, such as applications for playing games and watching movies. To further improve the response time, the single-pixel charging efficiency is investigated in this paper by optimizing the TFT dimensions in gate driver circuits in active-matrix liquid crystal displays. The accurate circuit simulation model is developed to minimize the signal’s fall time (Tf) by optimizing the TFT width-to-length ratio. Our results show that using a driving TFT width of 6790 μm and a reset TFT width of 640 μm resulted in a minimum Tf of 2.6572 μs, corresponding to a maximum pixel charging ratio of 90.61275%. These findings demonstrate the effectiveness of our optimization strategy in enhancing pixel charging efficiency and improving display performance.

Lightning is one of the frequent natural disasters, which seriously affects the secure and stable operation of the power system, especially the distribution network lines with weak reliability. In order to improve the power supply reliability of the distribution network, higher requirements are put forward for the accuracy of lightning warning. Therefore, this paper establishes a lightning warning model based on comprehensive multi-meteorological factor thresholds and analyzes the meteorological factor data such as atmospheric field strength, echo intensity, echo-top height, and vertical cumulative liquid water content under thunderstorm weather. The threshold value of each factor warning is obtained, and the corresponding threshold weight is calculated by the entropy weight method. According to the weight of each threshold, the comprehensive threshold index of lightning warning is obtained, and the lightning warning is based on this index. A total of 105 lightning data from May to June 2022 in Nanchang city were analyzed as samples. The thresholds of atmospheric field strength, echo intensity, echo-top height, and vertical cumulative liquid water content were 1.2 kV/m, 40 dBZ, 8 km, and 5.2 kg·m−2, respectively. The corresponding weights of each factor were 0.4188, 0.2056, 0.2105, and 0.165, respectively. This model was used to warn a thunderstorm event in July 2022 in Nanchang area. The success rate of the model warning was 0.91, the false alarm rate (FAR) was 0.11, and the critical success index (CSI) was 0.80. Compared with the single-factor threshold lightning warning model, the warning FAR is decreased by 6%, and CSI is increased by 14% while ensuring the high warning success rate.

Adenocarcinomas are one of the most common histological types of gastric cancer. It has been ranked fifth among common cancers and is the third among death causing cancers worldwide. The high mortality rate among patients with gastric cancer is because of its silent evolution, genetic heterogeneity, high resistance to chemotherapy as well as unavailability of highly effective therapeutic strategy. Until now a number of several treatment strategies have been developed and are being practiced such as surgery, chemotherapy, radio therapy, and immunotherapy, however, further developments are required to improve the treatment responses and reduce the side effects. Therefore, novel personal therapeutic strategies based on immunological responses should be developed by targeting different check points and key immune players. Targeting macrophages and related molecular elements can be useful to achieve these goals. In this minireview, we discuss the available treatment options, molecular underpinnings and immunological regulations associated with gastric adenocarcinoma. We further describe the possible check points and immunological targets that can be used to develop novel therapeutic options.

Abstract Long noncoding RNAs (lncRNAs) play important regulatory roles in a variety of pathological processes involving cancer. However, the exact molecular mechanisms of lncRNA regulation in endometrial carcinoma (EC) remain poorly defined. The aim of this study was to illustrate the mechanism of LINC00958 in regulating the function of IGF2BP3, an RNA binding protein involved in mRNA stability, and their clinical implications in EC. First, we investigated the clinical role of IGF2BP3 in EC and demonstrated its prognostic value. Loss-of-function and gain-of-function studies showed that IGF2BP3 promoted EC cell proliferation, migration and invasion. Then, we carried out RNA immunoprecipitation sequencing (RIP-seq) analysis, RNA pulldown and immunofluorescence-RNA fluorescence in situ hybridization to identify LINC00958 that interacted with IGF2BP3 in the cytoplasm of EC cells. Rescue experiments indicated that knockdown of LINC00958 partially offset the EC cell progression mediated by IGF2BP3. After that, RNA sequencing was used to screen out the downstream genes of IGF2BP3 and LINC00958. The results revealed that IGF2BP3 upregulated E2F3 expression by interacting with LINC00958. Furthermore, RNA stability assays demonstrated that silencing LINC00958 partially rescued the IGF2BP3-mediated promoting effect on the mRNA stability of E2F3. Collectively, this study suggests that LINC00958, as an oncogene, assists IGF2BP3 in stabilizing E2F3 mRNA and ultimately promotes EC progression, providing a promising therapeutic target for patients with EC.

BackgroundEndometrial cancer (EC) is a common gynecological cancer worldwide and the sixth most common female malignant tumor. A large number of studies conducted through database mining have identified many biomarkers that may be related to survival and prognosis. However, the predictive ability of single-gene biomarkers is not sufficiently accurate. In recent years, tumors have been shown to interact closely with their microenvironment, and tumor-infiltrating immune cells in the tumor microenvironment were associated with therapeutic effects. Furthermore, sequencing technology has evolved and allowed the identification of genetic signatures that may improve prediction results. The purpose of this research was to discover the Cancer Genome Atlas (TCGA) data to evaluate new genetic features that can predict the prognosis of EC.MethodsmRNA expression profiling was analyzed in patients with EC identified in the TCGA database (n = 530). Differentially expressed genes at different stages of EC were screened using the immune cell enrichment score (ImmuneScore). Univariate and multivariate Cox regression analyses was applied to evaluate genes significantly related to overall survival and establish the prognostic risk parameter formula. Kaplan–Meier survival curves and the logarithmic rank method were applied to verify the importance of risk parameters for the prognostic forecast. The accuracy of survival prediction was confirmed using the nomogram and Receiver Operating Characteristic (ROC) curve analysis. The mRNA expression of eight genes were measured by qRT-PCR. According to COX and HR values, NBAT1, a representative gene among 8 genes, was selected for CCK-8 assay, colony formation assay and transwell invasion assay to verify the effect on survival.ResultsEight related genes (NBAT1, GFRA4, PTPRT, DLX4, RANBP3L, UNQ6494, KLRB1, and PRAC1) were discovered to be significantly associated with the overall survival rate. According to these eight-gene signatures, 530 patients with EC were assigned to high- and low-risk subgroups. The prognostic capability of the eight-gene signature was not influenced by other elements.ConclusionsEight related gene markers were identified using ImmuneScore, which could predict prognosis and survival in patients with EC. These findings provide a basis for understanding the application of biological information in tumors and identifying the poor prognosis of EC.

Abstract Mitochondria are the powerhouse of eukaryotic cells, which regulate cell metabolism and differentiation. Recently, mitochondrial transfer between cells has been shown to direct recipient cell fate. However, it is unclear whether mitochondria can translocate to stem cells and whether this transfer alters stem cell fate. Here, mesenchymal stem cell (MSC) regulation is examined by macrophages in the bone marrow environment. It is found that macrophages promote osteogenic differentiation of MSCs by delivering mitochondria to MSCs. However, under osteoporotic conditions, macrophages with altered phenotypes, and metabolic statuses release oxidatively damaged mitochondria. Increased mitochondrial transfer of M1‐like macrophages to MSCs triggers a reactive oxygen species burst, which leads to metabolic remodeling. It is showed that abnormal metabolism in MSCs is caused by the abnormal succinate accumulation, which is a key factor in abnormal osteogenic differentiation. These results reveal that mitochondrial transfer from macrophages to MSCs allows metabolic crosstalk to regulate bone homeostasis. This mechanism identifies a potential target for the treatment of osteoporosis.

Abstract Endometrial cancer stem cells (ECSCs) play a vital role in endometrial cancer (EC) metastasis, relapse, and chemoresistance. However, the molecular mechanisms that sustain ECSCs remain elusive. Here, we showed that the expression of UPF1 was upregulated in EC tissues and ECSCs and correlated with poor clinicopathological characteristics. UPF1 silencing suppressed ECSC hallmarks, such as sphere formation ability, carboplatin resistance, migration and invasion, and cell cycle progression. UPF1 regulated the behavior and fate of ECSCs by stabilizing LINC00963. LINC00963 further shares the same miRNA response element with the core transcription factor SOX2 and relieved the suppression of SOX2 by miR-508-5p in self-renewing ECSCs. Notably, inhibition of UPF1 and LINC00963 in combination severely impaired the in vivo tumorigenic potential of ECSCs. We demonstrate that the UPF1/LINC00963/miR-508-5p/SOX2 axis has potential value in modulating ECSC maintenance, chemoresistance, and tumorigenesis in EC, which highlights a novel promising target for EC treatment.

At present, China is in the stage of the COVID-19 epidemic where regular prevention and control measures are required to contain the spread of disease. Reports of new sporadic cases are still widespread across China and medical personnel remain at high risk of exposure to infection. This is especially the case for medical staff working within emergency departments. Most gynecological emergency cases are complex and a high proportion require emergency surgical treatment. By referring to national regulations and requirements on COVID-19 prevention and control, and by summarizing our experiences in the battle against COVID-19 within Wuhan, this consensus report provides recommendations on the triage, reception, consultation, admission and surgical management of gynecological emergency patients. We also make suggestions for the environmental layout and disinfection and the medical waste management. This consensus aims to optimize the diagnosis and treatment process of gynecological emergency patients and reduce the exposure risk of medical staff within the current context of routine COVID-19 prevention and control.

Abstract Background Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma, lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. Methods We used qRT-PCR to detect the expression of MONC, miR-636 and GLCE in normal human endometrial tissues and endometrial carcinoma (EC) tissues. Luciferase assay was used to verify the binding sites between MONC and miR-636 and between miR-636 and GLCE. Double fluorescence in situ hybridization was used to locate MONC and miR-636 in cells. ECSCs were obtained by flow cytometry sorting assay. Sphere formation assay, CCK-8 assay, transwell invasion assay, cell cycle analysis and apoptosis assay were used to detect the effects of MONC/miR-636/GLCE axis on the malignant biological behavior of ECSCs and ECCs. The effect of MONC on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Finally, we conducted in vivo verification through Tumor xenografts in BALB/C nude mice. Results In this study, we found MONC is low expression in endometrial carcinoma (EC) and patients in the MONC high-expression group had a better prognosis. MONC and miR-636 are relatively co-localized in the cytoplasm. MONC directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3′-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC. Conclusions In conclusion, this study showed that MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. Thus the MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

The mammary gland is closely related to the female reproductive system in many aspects, affecting the whole gynecological system. Breast cancer (BC) is the most common malignancy in women and associated with considerable negative effects. Due to various factors including co-pathogenic genetic mutations, environment factors, lifestyle, behavioral factors, treatment regimens and in-creased survival of patients with BC, there is an increased probability of developing additional primary gynecologic cancers such as ovarian cancer (OC), endometrial cancer (EC), and cervical cancer (CC). More and more studies have been conducted in recent years. Multiple primary cancers (MPCs), also known as multiple primary malignancies, refers to two or more different primary cancers in the same patient occurring in the same or different organs or tissues. The pathogenesis of multiple primary cancers is complex and has a negative effect on the prognosis and survival of patients. This review discusses the common types of BC-associated MPCs, namely, BC associated with OC, BC associated with EC and BC associated with CC, as well as risk factors, pathogenesis, treatment, and prognosis of MPCs associated with breast and gynecologic cancers. It provides new intervention and treatment ideas for patients with BC-associated MPCs to improve quality of life and prognosis.

In recent years, Kubernetes (K8s) has become a dominant resource management and scheduling system in the cloud. In practical scenarios, short-running cloud workloads are usually scheduled through different scheduling algorithms provided by Kubernetes. For example, artificial intelligence (AI) workloads are scheduled through different Volcano scheduling algorithms, such as GANG_MRP, GANG_LRP, and GANG_BRA. One key challenge is that the selection of scheduling algorithms has considerable impacts on job performance results. However, it takes a prohibitively long time to select the optimal algorithm because applying one algorithm in one single job may take a few minutes to complete. This poses the urgent requirement of a simulator that can quickly evaluate the performance impacts of different algorithms, while also considering scheduling-related factors, such as cluster resources, job structures and scheduler configurations. In this paper, we design and implement a Kubernetes simulator called K8sSim, which incorporates typical Kubernetes and Volcano scheduling algorithms for both generic and AI workloads, and provides an accurate simulation of their scheduling process in real clusters. We use real cluster traces from Alibaba to evaluate the effectiveness of K8sSim, and the evaluation results show that (i) compared to the real cluster, K8sSim can accurately evaluate the performance of different scheduling algorithms with similar CloseRate (a novel metric we define to intuitively show the simulation accuracy), and (ii) it can also quickly obtain the scheduling results of different scheduling algorithms by accelerating the scheduling time by an average of 38.56×.

Abstract Background Hysteroscopy is a commonly used technique for diagnosing endometrial lesions. It is essential to develop an objective model to aid clinicians in lesion diagnosis, as each type of lesion has a distinct treatment, and judgments of hysteroscopists are relatively subjective. This study constructs a convolutional neural network model that can automatically classify endometrial lesions using hysteroscopic images as input. Methods All histopathologically confirmed endometrial lesion images were obtained from the Shengjing Hospital of China Medical University, including endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyps, and submucous myomas. The study included 1851 images from 454 patients. After the images were preprocessed (histogram equalization, addition of noise, rotations, and flips), a training set of 6478 images was input into a tuned VGGNet-16 model; 250 images were used as the test set to evaluate the model’s performance. Thereafter, we compared the model’s results with the diagnosis of gynecologists. Results The overall accuracy of the VGGNet-16 model in classifying endometrial lesions is 80.8%. Its sensitivity to endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyp, and submucous myoma is 84.0%, 68.0%, 78.0%, 94.0%, and 80.0%, respectively; for these diagnoses, the model’s specificity is 92.5%, 95.5%, 96.5%, 95.0%, and 96.5%, respectively. When classifying lesions as benign or as premalignant/malignant, the VGGNet-16 model’s accuracy, sensitivity, and specificity are 90.8%, 83.0%, and 96.0%, respectively. The diagnostic performance of the VGGNet-16 model is slightly better than that of the three gynecologists in both classification tasks. With the aid of the model, the overall accuracy of the diagnosis of endometrial lesions by gynecologists can be improved. Conclusions The VGGNet-16 model performs well in classifying endometrial lesions from hysteroscopic images and can provide objective diagnostic evidence for hysteroscopists.

Abstract Background Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC. Methods Based on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Results We analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs. Conclusions BTG1, as a tumor suppressor gene, plays an important role in the occurrence and development of EC. We believe that BTG1 can be used as a potential prognostic biomarker for EC.

Abstract Background HOXA cluster antisense RNA2 (HOXA-AS2), a long-chain non-coding RNA, plays an important role in the behavior of various malignant tumors. The roles of HOXA-AS2 in endometrial cancer remain unclear. Methods We test expression levels of HOXA-AS2, miRNA-302c-3p, the transcription factor zinc finger X-chromosomal protein (ZFX), and the chitinase-like protein YKL-40 in endometrial carcinoma by qRT-PCR and western blotting. Luciferase reporter and qRT-PCR assays were conducted to identify potential binding sites of HOXA-AS2 to miRNA-302c-3p. Cell cycle, migration and invasion ability of endometrial cancer cells were investigated using flow-cytometric analysis, CCK-8 and transwell assays, respectively. Results HOXA-AS2 levels were significantly increased in endometrial cancer specimens compared to normal endometrial specimens. Upregulated HOXA-AS2 promoted invasion and proliferation of type I endometrial cancer cells. HOXA-AS2 silenced miRNA-302c-3p by binding to it. MiRNA-302c-3p negatively regulates ZFX and YKL-40. Thus HOXA-AS2 promotes the development of type I endometrial cancer via miRNA-302c-3p-mediated regulation of ZFX. Conclusions These findings suggest that HOXA-AS2 can act as a new therapeutic target for type I endometrial cancer.

Abstract Background The preoperative peripheral blood neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have been reported to be associated with the prognosis of various cancers but are always discussed separately. The aim of this study is to bring the combination of NLR, PLR and MLR into the prognostic assessment system of endometrial cancer (EC) and establish a nomogram to provide an objective prediction model for clinical decisions. Methods A total of 1111 patients with EC who had accepted surgical treatment during 2013–2017 were involved in the analysis. Their NLR, PLR, and MLR levels were obtained from a routine blood examination within 2 weeks before operation. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs. Chi-square tests analysed the associations of the ratios with other clinicopathological variables. The prognostic value was indicated by overall survival (OS) via Cox proportional hazards models and Kaplan-Meier analysis. R software was used to establish the nomogram based on the combination of NLR, PLR, MLR and other clinicopathological factors. Results The median follow-up period was 40 months, and the median age was 56. The enrolled patients were stratified by cutoffs of 2.14 for NLR, 131.82 for PLR and 0.22 for MLR. Multivariate analyses demonstrated that high NLR over 2.14 (HR = 2.71, 95%CI = 1.83–4.02, P

Abstract Background To investigate the effect of transabdominal hysterectomy on the diversity of the intestinal flora in patients with uterine fibroids. Patients with uterine fibroids were selected from September 2018 to December 2018, in the Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, and stool specimens were collected from patients before and after surgery. Results High-throughput sequencing of the 16S rRNA gene was used to detect the changes in microbial community structure and diversity, and the effects of total hysterectomy on the intestinal flora were further analyzed. Estrogen levels decreased after trans-abdominal hysterectomy. High-throughput sequencing showed that after abdominal hysterectomy, the abundance and diversity of the intestinal flora decreased. The abundance changes were mainly due to Proteobacteria, where their abundance increased. Conclusions Trans-abdominal hysterectomy changes the intestinal flora of the body by lowering the level of estrogen in the body, which reduces the diversity and abundance of the intestinal flora.

Pancreatic cancer is a highly lethal gastrointestinal malignancy. Most patients are already in the middle to advanced stages of pancreatic cancer at the time of diagnosis and cannot be treated completely. As a single-atom planar two-dimensional crystal, graphene’s unusual electronic structure, specific electronic properties and excellent electron transport capacity make it uniquely advantageous in the field of electrochemical sensing. In this mini-review, we summarize the potential application of graphene in pancreatic cancer detection. K-Ras gene, CEA and MicroRNA are important in the early diagnosis of pancreatic cancer.

ObjectiveTo investigate variation in gut microbiome in female patients with invasive mole (IM) and choriocarcinoma (CC) and compare it with healthy controls.MethodsFecal microbiome of 12 female patients with IM, 9 female patients with CC, and 24 healthy females were analyzed based on 16s rDNA sequencing. Alpha (α) diversity was evaluated using Shannon diversity index and Pielou evenness index, while beta (β) diversity was assessed using principle coordinate analysis (PCoA) of unweighted Unifrac distances. The potential functional changes of microbiomes were predicted using Tax4Fun. The relative abundance of microbial taxa was compared using Welch’s t test. The role of varied gut microbiota was analyzed via receiver operating characteristic (ROC) curve.ResultsThe α diversity and β diversity were significantly different between IM patients and controls, but not between CC patients and controls. In addition, the abundance of cancer-related genes was significantly increased in IM and CC patients. Notably, a total of 19 families and 39 genera were found to have significant differences in bacterial abundance. ROC analysis indicated that Prevotella_7 may be a potential biomarker among IM, CC, and controls.ConclusionOur study demonstrated that the diversity and composition of gut microbiota among IM patients, CC patients, and healthy females were significantly different, which provides rationale for using gut microbiota as diagnostic markers and treatment targets, as well as for further study of gut microbiota in gestational trophoblastic neoplasia (GTN).

Abstract Uterine corpus endometrial carcinoma (UCEC) is frequently diagnosed among women worldwide. However, there are different prognostic outcomes because of heterogeneity. Thus, the aim of the current study was to identify a gene signature that can predict the prognosis of patients with UCEC. UCEC gene expression profiles were first downloaded from the The Cancer Genome Atlas (TCGA) database. After data processing and forward screening, 11 390 key genes were selected. The UCEC samples were randomly divided into training and testing sets. In total, 996 genes with prognostic value were then examined by univariate Cox survival analysis with a P‐value

Long non-coding RNAs (LncRNAs) can bind to other proteins or RNAs to regulate gene expression, and its role in tumors has been extensively studied. A common RNA binding protein, UPF1, is also a key factor in a variety of RNA decay pathways. RNA decay pathways serve to control levels of particular RNA molecules. The expression of UPF1 is often dysregulated in tumors, an observation which suggests that UPF1 contributes to development of a variety of tumors. Herein, we review evidence from studies of fourteen lncRNAs interact with UPF1. The interaction between lncRNA and UPFI provide fundamental basis for cell transformation and tumorigenic growth.

BackgroundBesides being one of the most prevalent cancers among women, incidence and mortality rates of endometrial cancer (EC) are still increasing. The E2F family of transcriptional factors is involved in cell differentiation, apoptosis, and inhibition of DNA damage response, thus affecting growth and invasion of tumor cells.MethodsWe used multiple bioinformatics tools to explore the role of E2F family in endometrial cancer.ResultsThe expression of E2F1/2/3/7/8 was significantly upregulated in endometrial cancer tissues, converse to E2F4, which was downregulated. Methylation downregulates all E2Fs except for E2F2. Accordingly, E2F1/2/3/5/7/8 are potential diagnostic biomarkers for EC. In particular, EC patients displaying upregulated E2F1, and E2F3 expression had a worse overall survival and relapse-free survival. E2F8, E2F7, and E2F1 were the top three, most-frequently altered genes in endometrial cancer. E2F family activates apoptosis pathways, regulates cell cycle, and impairs DNA damage response pathways. Drug-sensitivity analysis demonstrated that the level of E2F2/3/8 negatively correlated with drug resistance. Meanwhile, immune infiltrations analysis revealed that E2F family is associated with recruitment of several immune cells. Enrichment analysis on its part revealed that the E2F family is mainly associated with cell cycle, sequence-specific DNA binding, nuclear transcription factor complex, PI3K-Akt signaling, and p53 signaling pathway. We also identified multiple E2Fs-associated miRNA and kinase targets in endometrial cancer.ConclusionOur study revealed the unique expression signature and clinical significance of E2F family in EC, demonstrating the potential clinical utility of these transcription factors (TF) in endometrial cancer.

The finite element method (FEM) has been applied to extract the coupling-of-modes (COM) parameters of surface acoustic wave (SAW) devices for a long time. It always involves calculating the dispersive curves or harmonic admittance, which makes the extraction process and results sophisticated, time-consuming and inaccurate. Therefore, a simple method is proposed to extract all COM parameters of the SAW devices rapidly and accurately in this paper. It is based on the FEM and combines the stationary analysis with modal analysis. We have described in detail the basic principles and procedures of the proposed method, and made a comprehensive comparison between the proposed method and the other two existing methods. We have also examined the proposed method by extracting COM parameters of some common SAW substrate, and compared our extracted results with those reported in the other literatures. Results show that our proposed method holds higher accuracy and more efficiency (~s order) than the others (~h order). Moreover, our extracted COM parameters are in an excellent agreement with those reported in the other literatures.

Ovarian cancer (OC) is the most malignant tumor in the female reproductive tract. Although abundant molecular biomarkers have been identified, a robust and accurate gene expression signature is still essential to assist oncologists in evaluating the prognosis of OC patients. In this study, samples from 367 patients in The Cancer Genome Atlas (TCGA) database were subjected to mRNA expression profiling. Then, we used a gene set enrichment analysis (GSEA) to screen genes correlated with epithelial–mesenchymal transition (EMT) and assess their prognostic power with a Cox proportional regression model. Six genes (TGFBI, SFRP1, COL16A1, THY1, PPIB, BGN) associated with overall survival (OS) were used to construct a risk assessment model, after which the patients were divided into high-risk and low-risk groups. The six-gene signature was an independent prognostic biomarker of OS for OC patients based on the multivariate Cox regression analysis. In addition, the six-gene model was validated with samples from the Gene Expression Omnibus (GEO) database. In summary, we established a six-gene signature relevant to the prognosis of OC, which might become a therapeutic tool with clinical applications in the future.

Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models. In vitro, fenestrae of primary LSECs gradually shrank, along with the down-regulation of the NO-dependent pathway and the augment of the AMPK-dependent autophagy; these effects were aggravated by rapamycin (an autophagy activator) or aldosterone treatment. Additionally, aldosterone increased oxidation mediated by Cav1, reduced ATP generation, and subsequently induced the AMPK-dependent autophagy, leading to the down-regulation of the NO-dependent pathway and LSECs defenestration. These effects were reversed by MR antagonist spironolactone, antioxidants or autophagy inhibitors. Besides, aldosterone enhanced the co-immunoprecipitation of Cav1 with p62 and ubiquitin, and induced Cav1 co-immunofluorescence staining with LC3, ubiquitin, and F-actin in the perinuclear area of LSECs. Furthermore, aldosterone treatment increased the membrane protein level of Cav1, whereas decrease the cytoplasmic protein level of Cav1, indicating that aldosterone induced Cav1-related selective autophagy and F-actin remodeling to promote defenestration. Consequently, Cav1-related selective autophagy initiated by aldosterone-induced oxidation promotes LSECs defenestration via activating the AMPK-ULK1 pathway and inhibiting the NO-dependent pathway.

This paper presents a passive wireless pillar load measurement method based on surface acoustic wave (SAW) technology. A strain transfer mechanical structure was designed, and the strain distribution of an elastic substrate was analyzed using elastic thin plate bending theory. In addition, the relationship between the strain and frequency shift of the SAW resonator (SAWR) was analyzed, and a strain sensitivity numerical analysis using different bonding directions was performed. Results corroborated that the differential structure of resonators, one of which is placed at the edge along the direction of a diameter and the other is placed at the center with an angle of 45° to the diameter, is a suitable form of the SAW load sensors. Moreover, the SAWR parameters were optimized to obtain a high-performance resonator. Furthermore, The SAWRs and strain transfer mechanical structures were manufactured, the pillar load measurement system was set, and the proposed SAW load measurement method was evaluated. Experimental results affirmed that the load sensitivity is 8.64 kHz/kN. The SAW pillar load method is feasible for practical application.

Background The objective of this study is to investigate small cell neuroendocrine carcinoma of the cervix (SCCC), using a retrospective clinicopathological characteristic and treatment approach. Method We retrospectively analyzed cases of early-stage SCCC, identified between 2006 and 2016, in women who received radical surgery and adjuvant chemotherapy with or without radiotherapy. Kaplan–Meier and one-way ANOVA analyses were performed. Result A total of 37 cases of SCCC are presented in this study, of which 21 had stage IB1 SCCC, 12 had stage IB2, 3 had stage IIA1, and 1 had stage IIA2. All patients were treated with radical surgery and adjuvant chemotherapy, specifically, 26 with radical surgery followed by adjuvant chemotherapy plus radiation and 11 with neoadjuvant chemotherapy (NACT) followed by radical surgery. After a median follow-up time of 27 months (range, 8–115 months), the 2-year and 5-year disease-free survival rate for all patients was 51.9% and 34.1%, respectively, and the overall survival rate was 60.3% and 38.6%, respectively. Univariate analysis showed that International Federation of Gynecology and Obstetrics (FIGO) stage and tumor size may be a predictor of a poor prognosis. NACT and adjuvant radiation did not improve survival over adjuvant chemotherapy alone but should not be a significant independent prognostic factor for survival. Conclusion Even in patients with early-stage SCCC, the prognosis is poor, although FIGO stage and tumor size may act as surrogate factors prognostic of survival.

A high-sensitive thickness shear mode film bulk acoustic resonator pressure sensor based on lateral field excitation is designed with its structure simulated in environment of air and liquids. A finite element model of film bulk acoustic resonator pressure sensor structure is established to obtain frequency variation under different pressure conditions by parameter sweep method when the multi-physics fields are added to the model. The results of simulation show that the pressure sensor’s resonance frequency is 2.114 GHz and pressure sensitivity is 1200 Hz/kPa in air. In liquid environment, film bulk acoustic resonator pressure sensor displays a pressure sensitivity of 325 Hz/kPa in ethanol, 475 Hz/kPa in deionized water, and 612.5 Hz/kPa in glycerol. This film bulk acoustic resonator pressure sensor has been proved to be highly sensitive both in air and liquid environment and has the potential to be used in biomedical applications.

Background/Aims: The aggressive manner of ovarian cancer (OVC) cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF) promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. Methods: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. Results: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF-overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. Conclusion: PLGF enhances OVC cell invasion through MAPK-p38-dependent activation of ZEB2.

Background/Aims: Elucidation of the molecular mechanisms underlying ovarian cancer (OC) cell invasion and migration may provide important evidence for developing efficient therapy. Recently, Matrix metalloproteinase (MMP) has been shown to be regulated by vascular endothelial growth factor family members, especially placental growth factor (PLGF), as a potential mechanism underlying cancer invasion. Here, we studied the molecular relationship between PLGF and MMP7 in the OC. Methods: We examined the levels of PLGF and MMP7 in the resected OC specimens and compared to paired adjacent non-tumor ovarian tissue. We also examined the correlation between PLGF and MMP7. We modified PLGF levels in a human OC cell line, OVCAR3, and analyzed the effects on MMP7. Prediction of microRNA (miRNA) binding to 3'-UTR of MMP7 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay using miR-543-modifed OC cells. The levels of miR-543 were examined in the OC specimens, and the correlation between miR-543 and PLGF or MMP7 was performed. Results: PLGF and MMP7 both significantly increased in the OC specimens, compared to paired adjacent non-tumor ovarian tissue. PLGF significantly increased MMP7 in the OC cells at protein level, but not at mRNA level. In OC cells, PLGF significantly decreased the levels of miR-543, which suppressed the translation of MMP7 mRNA via 3'-UTR binding. In OC specimen, miR-543 significantly decreased, compared to paired adjacent non-tumor ovarian tissue. An inverse correlation was detected between the levels of miR-543 and PLGF or MMP7 in the OC specimens. Conclusion: MiR-543 inhibits translation of MMP7 through binding to the 3'-UTR of MMP7 mRNA in OC. PLGF suppresses miR-543, which activates MMP7-mediated cancer invasion.

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