The role of hydrogen-rich water in delaying the pulp breakdown of litchi fruit during postharvest storage.

Previous studies have indicated that hydrogen-rich water (HW) treatment can delay fruit ripening and senescence. However, little is known about the HW-delaying pulp breakdown. In this study, eight physiological characteristics revealed that HW treatment delayed both pericarp browning and pulp breakdown of litchi fruit. To gain a comprehensive understanding of the changes in litchi pulp, a combination of multiple metabolomics and gene expression analyses was conducted, assessing 67 primary metabolites, 103 volatiles, 31 amino acids, and 13 crucial metabolite-related genes. Results showed that HW treatment promoted starch degradation, decelerated cell wall degradation and glycolysis, and maintained the flavor and quality of litchi fruit. Furthermore, HW treatment stimulated the production of volatile alcohols, aldehydes, ketones, olefins, and amino acids, which might play a vital role in HW-delaying pulp breakdown. This study sheds light on the mechanism by which HW delayed pulp breakdown by investigating small molecule metabolites and metabolic pathways.

An Improved Theory for Designing and Numerically Calibrating Circular Touch Mode Capacitive Pressure Sensors.

The design, especially the numerical calibration, of a circular touch mode capacitive pressure sensor is highly dependent on the accuracy of the analytical solution of the contact problem between the circular conductive membrane and the rigid plate of the sensor. In this paper, the plate/membrane contact problem is reformulated using a more accurate in-plane equilibrium equation, and a new and more accurate analytical solution is presented. On this basis, the design and numerical calibration theory for circular touch mode capacitive pressure sensors has been greatly improved and perfected. The analytical relationships of pressure and capacitance are numerically calculated using the new and previous analytical solutions, and the gradually increasing difference between the two numerical calculation results with the gradual increase in the applied pressure is graphically shown. How to use analytical solutions and analytical relationships to design and numerically calibrate a circular touch mode capacitive pressure sensor with a specified pressure detecting range is illustrated in detail. The effect of changing design parameters on capacitance-pressure analytical relationships is comprehensively investigated; thus, the direction of changing design parameters to meet the required or desired range of pressure or capacitance is clarified.

CIFG-Net: Cross-level information fusion and guidance network for Polyp Segmentation.

Colorectal cancer is a common malignant tumor of the digestive tract. Most colorectal cancer is caused by colorectal polyp lesions. Timely detection and removal of colorectal polyps can substantially reduce the incidence of colorectal cancer. Accurate polyp segmentation can provide important polyp information that can aid in the early diagnosis and treatment of colorectal cancer. However, polyps of the same type can vary in texture, color, and even size. Furthermore, some polyps are similar in colour to the surrounding healthy tissue, which makes the boundary between the polyp and the surrounding area unclear. In order to overcome the issues of inaccurate polyp localization and unclear boundary segmentation, we propose a polyp segmentation network based on cross-level information fusion and guidance. We use a Transformer encoder to extract a more robust feature representation. In addition, to refine the processing of feature information from encoders, we propose the edge feature processing module (EFPM) and the cross-level information processing module (CIPM). EFPM is used to focus on the boundary information in polyp features. After processing each feature, EFPM can obtain clear and accurate polyp boundary features, which can mitigate unclear boundary segmentation. CIPM is used to aggregate and process multi-scale features transmitted by various encoder layers and to solve the problem of inaccurate polyp location by using multi-level features to obtain the location information of polyps. In order to better use the processed features to optimise our segmentation effect, we also propose an information guidance module (IGM) to integrate the processed features of EFPM and CIPM to obtain accurate positioning and segmentation of polyps. Through experiments on five public polyp datasets using six metrics, it was demonstrated that the proposed network has better robustness and more accurate segmentation effect. Compared with other advanced algorithms, CIFG-Net has superior performance. Code available at: https://github.com/zspnb/CIFG-Net.

Dietary fiber intake and cognitive impairment in older patients with chronic kidney disease in the United States: A cross-sectional study.

BACKGROUND: High-fiber diet has been associated with better cognitive performance. However, the association between dietary fiber intake and cognition in older patients with chronic kidney disease (CKD) remains unknown. Hence, this study aimed to investigate the effect of dietary fiber intake on cognition in older patients with CKD. METHODS: This study included participants aged ≥60 years who provided data on social demography, cognitive tests (Consortium to Establish a Registry for Alzheimer's disease Word Learning [CERAD-WL], CERAD Delayed Recall [CERAD-DR], Animal Fluency Test [AFT], and Digit Symbol Substitution Test [DSST]), diet, and other potential cognition-related variables from the National Health and Nutrition Examination Survey 2011-2014. Fully-adjusted multivariate logistic regression subgroup models were performed, and multiple linear regression analyses were employed to examine the association between dietary fiber intake and cognition in patients with CKD. RESULTS: A total of 2461 older adults were included, with 32% who suffered from CKD. Participants with CKD scored lower in CERAD-WL, CERAD-DR, AFT, and DSST. Patients with CKD consuming low dietary fiber (≤25 g/day) had a higher risk of CERAD-WL and DSST impairments. High dietary fiber intake eliminated the differences in CERAD-WL and DSST impairments between the CKD and non-CKD participants. However, no associations were observed between CKD and CERAD-DR and AFT impairments regardless of dietary fiber intake. A positive linear relationship between dietary fiber intake and AFT score was observed in older patients with CKD. CONCLUSION: High dietary fiber intake may benefit cognitive function in older patients with CKD. High-fiber diet management strategies could potentially mitigate cognitive impairment in this group of patients.

IFI27 Integrates Succinate and Fatty Acid Oxidation to Promote Adipocyte Thermogenic Adaption.

Mitochondria are the pivot organelles to control metabolism and energy homeostasis. The capacity of mitochondrial metabolic adaptions to cold stress is essential for adipocyte thermogenesis. How brown adipocytes keep mitochondrial fitness upon a challenge of cold-induced oxidative stress has not been well characterized. This manuscript shows that IFI27 plays an important role in cristae morphogenesis, keeping intact succinate dehydrogenase (SDH) function and active fatty acid oxidation to sustain thermogenesis in brown adipocytes. IFI27 protein interaction map identifies SDHB and HADHA as its binding partners. IFI27 physically links SDHB to chaperone TNF receptor associated protein 1 (TRAP1), which shields SDHB from oxidative damage-triggered degradation. Moreover, IFI27 increases hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA) catalytic activity in ß-oxidation pathway. The reduced SDH level and fatty acid oxidation in Ifi27-knockout brown fat results in impaired oxygen consumption and defective thermogenesis. Thus, IFI27 is a novel regulator of mitochondrial metabolism and thermogenesis.

An analysis of the relationship of blood pressure and its variability with residual kidney function loss in hemodialysis patients.

AIMS: This study aims to investigate the relationship of blood pressure (BP) and systolic BP (SBP) variability with residual kidney function (RKF) loss in hemodialysis (HD) patients. MATERIALS AND METHODS: The demographic and clinical information and data on RKF loss events in HD patients were collected. The baseline characteristics of the patients were compared among groups according to pre- and postdialysis SBP (< 120, 120 - 139, 140 - 159, and ≥ 160 mmHg) and diastolic BP (DBP) (< 80, 80 - 89, 90 - 99, and ≥ 1 00 mmHg). Participants were divided into two groups based on the mean intradialytic and interdialytic SBP variability. Kaplan-Meier analysis and Cox regression analysis were used to evaluate the risk of RKF loss. RESULTS: A total of 157 participants with an average HD vintage of 35.97 months were included. The group with the lowest predialysis SBP showed the longest duration of residual urine. However, Kaplan-Meier analysis and Cox regression analysis indicated that BP and SBP variability were not independent risk factors for RKF loss. Higher serum albumin levels showed protective effects against RKF loss, and diabetes mellitus (DM) and higher serum calcium were the independent risk factors for RKF loss. CONCLUSION: BP and SBP variability were not independent risk factors for RKF loss in HD patients. DM, serum albumin, and calcium were independent factors related to RKF loss.

MyoPS: A benchmark of myocardial pathology segmentation combining three-sequence cardiac magnetic resonance images.

Assessment of myocardial viability is essential in diagnosis and treatment management of patients suffering from myocardial infarction, and classification of pathology on the myocardium is the key to this assessment. This work defines a new task of medical image analysis, i.e., to perform myocardial pathology segmentation (MyoPS) combining three-sequence cardiac magnetic resonance (CMR) images, which was first proposed in the MyoPS challenge, in conjunction with MICCAI 2020. Note that MyoPS refers to both myocardial pathology segmentation and the challenge in this paper. The challenge provided 45 paired and pre-aligned CMR images, allowing algorithms to combine the complementary information from the three CMR sequences for pathology segmentation. In this article, we provide details of the challenge, survey the works from fifteen participants and interpret their methods according to five aspects, i.e., preprocessing, data augmentation, learning strategy, model architecture and post-processing. In addition, we analyze the results with respect to different factors, in order to examine the key obstacles and explore the potential of solutions, as well as to provide a benchmark for future research. The average Dice scores of submitted algorithms were 0.614±0.231 and 0.644±0.153 for myocardial scars and edema, respectively. We conclude that while promising results have been reported, the research is still in the early stage, and more in-depth exploration is needed before a successful application to the clinics. MyoPS data and evaluation tool continue to be publicly available upon registration via its homepage (www.sdspeople.fudan.edu.cn/zhuangxiahai/0/myops20/).

CXCL8 delivered by plasma-derived exosomes induces the symptoms of post-traumatic stress disorder through facilitating astrocyte-neuron communication.

Extracellular vesicles (EVs) play an important role in post-traumatic stress disorder (PTSD). This study is aimed to investigate the possible molecular mechanism of CD63 mediating CXCL8 delivery via EVs to affect astrocyte-neuron communication in PTSD. The neuron-derived EVs (NDEVs) and astrocyte-derived EVs (ADEVs) were isolated from plasma in PTSD patients. Next, the uptake of EVs by neurons was assessed. Following determination of the interaction between CD63 and CXCL8, gain- and loss-of-function experiments were performed in astrocytes. Finally, a PTSD mouse model was established using the single prolonged stress and electric foot shock to confirm the effects of plasma-derived EVs delivering CXCL8 on anxiety- and depression-like behaviors in PTSD mice. EVs derived from plasma of PTSD patients aggravated anxiety- and depression-like behaviors in PTSD mice. CXCL8 was a key gene upregulated in both NDEVs and ADEVs from plasma of PTSD patients, which could be delivered into EVs by CD63. Meanwhile, CXCL8 was also highly expressed in plasma-derived EVs. In vivo experiments also verified that plasma-derived EVs could enhance astrocyte-neuron communication by delivering CXCL8, and silencing of CXCL8 ameliorated anxiety- and depression-like behaviors in PTSD mice. Taken together, CD63 promotes delivery of CXCL8 via EVs to induce PTSD by enhancing astrocyte-neuron communication, suggesting the potential of CD63 mediating delivery of CXCL8 via EVs as a therapeutic target for PTSD.

Deletion of BACH1 alleviates ferroptosis and protects against LPS-triggered acute lung injury by activating Nrf2/HO-1 signaling pathway.

Multiple lines of evidences have unraveled the emerging role of ferroptosis in the pathophysiological process of acute lung injury (ALI). In this study, we aimed to decipher the role of BACH1 in the onset and progression of ALI with a focus on ferroptosis and elucidated potential molecular mechanism. We observed that BACH1 expression was drastically elevated in BEAS-2B cells upon exposure to LPS. In the functional aspect, BACH1 deletion exerted an anti-inflammatory property, featured by decreased the secretion of several cytokines including TNF-α, IL-1ß and IL-6 in the face of LPS challenge. What's more important, BACH1 knockout evidently repressed LPS-triggered oxidative stress damage, as evidenced by reduced reactive oxygen species (ROS) production and malondialdehyde (MDA) generation, accompanied with the elevated the activities of superoxide dismutase (SOD), GSH-Px and CAT. Meanwhile, ablation of BACH1 restrained LPS-elicited ferroptosis, as characterized by decreased iron content and PTGS2 expression, accompanied with increased expression of SLC7A11 and GPX4. In terms of mechanism, Nrf2/HO-1 signaling inhibitor effectively abrogated the beneficial effects of BACH1 inhibition on LPS-stimulated inflammation, oxidative damage and ferroptosis. Taken together, these preceding outcomes strongly illuminated that BACH1 was a novel regulator of LPS-evoked injury through regulation of inflammation response, oxidative stress and ferroptosis via activation Nrf2/HO-1 signaling, indicating that BACH1 may represent as a promising novel therapeutic candidate for ALI treatment.

microRNA-100 shuttled by human umbilical cord MSC-secreted extracellular vesicles induces endometriosis by inhibiting HS3ST2.

In recent years, the function of human umbilical cord mesenchymal stem cell-originated extracellular vesicles (hUC-MSC-EVs) on endometriosis has been reported, while its specific mechanisms remain largely unknown. This study aimed at investigating the mechanisms underlying the modulation of EVs harboring miR-100 derived from hUC-MSCs in the growth dynamics of endometrial stromal cells in endometriosis. Endometriosis mouse models were established. miR-100 was upregulated and HS3ST2 was downregulated in endometriosis. Ectopic endometrial tissues and umbilical cord tissues were obtained to extract endometrial stromal cells and hUC-MSCs, from which EVs were isolated. Next, the endometrial stromal cells were co-cultured with hUC-MSC-EVs, during which gain- or loss-of-function approaches were employed for gene overexpression or silencing. The binding affinity among miR-100 and HS3ST2 was identified using multiple assays. It was unveiled that miR-100 could target and inhibit HS3ST2. miR-100 from hUC-MSCs could be transferred into the endometrial stromal cells via EVs. Moreover, miR-100 shuttled by hUC-MSC-EVs facilitated endometrial stromal cell proliferation, invasion, and migration, as well as EMT by inhibiting HS3ST2. In vivo experiments also confirmed that hUC-MSC-derived EVs carrying miR-100 induced the occurrence and development of endometriosis. Collectively, hUC-MSC-EV-loaded miR-100 downregulated HS3ST2 to facilitate the development of endometriosis, which highlights a promising therapeutic target for treating endometriosis.

Complete mitochondrial genomes of Thyreophagus entomophagus and Acarus siro (Sarcoptiformes: Astigmatina) provide insight into mitogenome features, evolution, and phylogeny among Acaroidea mites.

Mites from the Acaroidea (Sarcoptiformes: Astigmatina) are important pests of various stored products, posing potential threats to preserved foods. In addition, mites can cause allergic diseases. Complete mitochondrial genomes (mitogenomes) are valuable resources for different research fields, including comparative genomics, molecular evolutionary analysis, and phylogenetic inference. We sequenced and annotated the complete mitogenomes of Thyreophagus entomophagus and Acarus siro. A comparative analysis was made between mitogenomic sequences from 10 species representing nine genera within Acaroidea. The mitogenomes of T. entomophagus and A. siro contained 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region. In Acaroidea species, mitogenomes have highly conserved gene size and order, and codon usage. Among Acaroidea mites, most PCGs were found to be under purifying selection, implying that most PCGs might have evolved slowly. Our findings showed that nad4 evolved most rapidly, whereas cox1 and cox3 evolved most slowly. The evolutionary rates of Acaroidea vary considerably across families. In addition, selection analyses were also performed in 23 astigmatid mite species, and the evolutionary rate of the same genes in different superfamilies exhibited large differences. Phylogenetic results are mostly consistent with those identified by previous phylogenetic studies on astigmatid mites. The monophyly of Acaroidea was rejected, and the Suidasiidae and Lardoglyphidae appeared to deviate from the Acaroidea branch. Our research proposed a review of the current Acaroidea classification system.

Fast and accurate measurement of the polarization-dependent detection efficiency of superconducting nanowire single photon detectors.

Superconducting nanowire single photon detectors (SNSPDs) have been extensively investigated due to their superior characteristics, including high system detection efficiency, low dark count rate and short recovery time. The polarization sensitivity introduced by the meandering-type superconductor nanowires is an intrinsic property of SNSPD, which is normally measured by sweeping hundreds of points on the Poincaré sphere to overcome the unknown birefringent problem of the SNSPD's delivery fiber. In this paper, we propose an alternative method to characterize the optical absorptance of SNSPDs, without sweeping hundreds of points on the Poincaré sphere. It is shown theoretically that measurements on the system detection efficiencies (SDEs) subject to cases of four specific photon polarization states are sufficient to reveal the two eigen-absorptances of the SNSPD. We validate the proposed method by comparing the measured detection spectra with the spectra attained from sweeping points on the Poincaré sphere and the simulated absorption spectra.

Polymer Conductive Membrane-Based Circular Capacitive Pressure Sensors from Non-Touch Mode of Operation to Touch Mode of Operation: An Analytical Solution-Based Method for Design and Numerical Calibration.

Polymer-based conductive membranes play an important role in the development of elastic deflection-based pressure sensors. In this paper, an analytical solution-based method is presented for the design and numerical calibration of polymer conductive membrane-based circular capacitive pressure sensors from non-touch mode of operation to touch mode of operation. The contact problem of a circular membrane in frictionless contact with a rigid flat plate under pressure is analytically solved, and its analytical solution is used for the design of touch mode circular capacitive pressure sensors for the first time. The analytical relationship with input pressure as independent variable and output capacitance as dependent variable is precisely derived and is used for the numerical calibrations of the analytical relationships with input capacitance as the independent variable and output pressure as the dependent variable in order to meet the capacitive pressure sensor mechanism of detecting pressure by measuring capacitance. For the first time, an example showing the design and numerical calibration of a given (given design parameters) polymer conductive membrane-based circular capacitive pressure sensor from non-touch mode of operation to touch mode of operation is provided. Then, the influence of changing several important design parameters on input capacitance-output pressure relationships is comprehensively investigated in order to clarify the desired input-output relationships when changing design parameters.

Polymer Conductive Membrane-Based Non-Touch Mode Circular Capacitive Pressure Sensors: An Analytical Solution-Based Method for Design and Numerical Calibration.

In this paper, an analytical solution-based method for the design and numerical calibration of polymer conductive membrane-based non-touch mode circular capacitive pressure sensors is presented. The accurate analytical relationship between the capacitance and applied pressure of the sensors is derived by using the analytical solution for the elastic behavior of the circular polymer conductive membranes under pressure. Based on numerical calculations using the accurate analytical relationship and the analytical solution, the analytical relationship between the pressure as output and the capacitance as input, which is necessary to achieve the capacitive pressure sensor mechanism of detecting pressure by measuring capacitance, is accurately established by least-squares data fitting. An example of how to arrive at the design and numerical calibration of a non-touch mode circular capacitive pressure sensor is first given. Then, the influence of changing design parameters such as membrane thickness and Young's modulus of elasticity on input-output relationships is investigated, thus clarifying the direction of approaching the desired input-output relationships by changing design parameters.

Association between the Platelet-Derived Growth Factor/Platelet-Derived Growth Factor Receptor System and Risk of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

This research examines the association between the platelet-derived growth factor/platelet-derived growth factor receptor (PDGF/PDGFR) system and rheumatoid arthritis (RA) susceptibility through a comprehensive search of the PubMed database to study the expression of the PDGF/PDGFR system in RA. Review Manager software version 5.3 was used for statistical analysis. Six eligible studies published in the English language were included, including 108 rheumatoid arthritis cases and 85 controls with the corresponding 126 and 97 tests, respectively, relating the expression of the PDGF/PDGFR system to the risk of RA. The overall results indicated a significant association between the PDGF/PDGFR system expression and RA (OR = 5.25, 95% CI: 3.00-9.18, p < 00001), RA patients in Asian countries (OR = 4.13, 95% CI = 2.04-8.39, p < 0.0001) and in Western countries (OR = 9.18, 95% CI = 2.04-8.39, p = 0.03), and only PDGF expression in RA patients (OR = 5.28, 95% CI = 2.73-10.21, p < 0.00001). Thus, only the PDGFR expression was insignificantly associated with RA susceptibility (OR = 9.25, 95% CI = 0.63-136.30, p = 0.11). Hence, the PDGF/PDGFR system most likely contributes to susceptibility to RA.

RPS-Net: An effective retinal image projection segmentation network for retinal vessels and foveal avascular zone based on OCTA data.

BACKGROUND: Optical coherence tomography angiography (OCTA) is an advanced imaging technology that can present the three-dimensional (3D) structure of retinal vessels (RVs). Quantitative analysis of retinal vessel density and foveal avascular zone (FAZ) area is of great significance in clinical diagnosis, and the automatic semantic segmentation at the pixel level helps quantitative analysis. The existing segmentation methods cannot effectively use the volume data and projection map data of the OCTA image at the same time and lack the trade-off between global perception and local details, which lead to problems such as discontinuity of segmentation results and deviation of morphological estimation. PURPOSE: In order to better assist physicians in clinical diagnosis and treatment, the segmentation accuracy of RVs and FAZ needs to be further improved. In this work, we propose an effective retinal image projection segmentation network (RPS-Net) to achieve accurate RVs and FAZ segmentation. Experiments show that this network exhibits good performance and outperforms other existing methods. METHODS: Our method considers three aspects. First, we use two parallel projection paths to learn global perceptual features and local supplementary details. Second, we use the dual-way projection learning module to reduce the depth of the 3D data and learn image spatial features. Finally, we merged the two-dimensional features learned from the volume data with the two-dimensional projection data, and used a U-shaped network to further learn and generate the final result. RESULTS: We validated our model on the OCTA-500, which is a large multi-modal, multi-task retinal dataset. The experimental results showed that our method achieved state-of-the-art performance; the mean Dice coefficients for RVs are 89.89 ± 2.60 (%) and 91.40 ± 9.18 (%) on the two subsets, while the Dice coefficients for FAZ are 91.55 ± 2.05 (%) and 97.80 ± 2.75 (%), respectively. CONCLUSIONS: Our method can make full use of the information of 3D data and 2D data to generate segmented images with higher continuity and accuracy. Code is available at https://github.com/hchuanZ/MFFN/tree/master.

Research Progress of PARP Inhibitor Monotherapy and Combination Therapy for Endometrial Cancer.

Endometrial cancer is one of the three most common malignant tumors in the female reproductive system. Advanced and recurrent endometrial cancers have poor prognoses and lack effective treatments. Poly (ADP-ribose) polymerase (PARP) inhibitors have been applied to many different types of tumors, and they can selectively kill tumor cells that are defective in homologous recombination repair. Endometrial cancer is characterized by mutations in homologous recombination repair genes; accordingly, PARP inhibitors have achieved positive results in off-label treatments of endometrial cancer cases. Clinical trials of PARP inhibitors as monotherapies and within combination therapies for endometrial cancer are ongoing. For this review, we searched PubMed with "endometrial cancer" and "PARP inhibitor" as keywords, and we used "olaparib", "rucaparib", "niraparib" and "talazoparib" as search terms in clinicaltrials.gov for ongoing trials. The literature search ended in October 2020, and only English-language publications were selected. Multiple studies confirm that PARP inhibitors play an important role in killing tumor cells with defects in homologous recombination repair. Its combination with immune checkpoint inhibitors, PI3K/AKT/mTOR pathway inhibitors, cell cycle checkpoint inhibitors, and other drugs can improve the treatment of endometrial cancer.

LncRNA MAFG-AS1 promotes the malignant phenotype of ovarian cancer by upregulating NFKB1-dependent IGF1.

Long non-coding RNAs (lncRNAs) were recently recognized to vitally function in a variety of cancer cellular events, including epithelial-mesenchymal transition (EMT), invasion, and migration, particularly in ovarian cancer (OC). Herein, we sought to investigate the potential role of MAFG-AS1 in the malignant behaviors of OC cells. The binding affinity between MAFG-AS1, miR-339-5p, NFKB1 or IGF1 was characterized so as to identify the underlying mechanism of corresponding their interactions. We conducted MAFG-AS1 overexpression or knockdown along with NFKB1 and IGF1 silencing to examine their effects on the EMT, migration, and invasion of OC cells. Tumors were xenografted in nude mice to validate the in vitro findings. Our data showed significantly high expression pattern of MAFG-AS1 in the OC tissues and cells. Further mechanistic investigations revealed that MAFG-AS1 upregulated the IGF1 expression pattern through recruitment of NFKB1, whereas MAFG-AS1 upregulated the NFKB1 expression pattern through binding to miR-339-5p. Thus, MAFG-AS1 overexpression accelerated the EMT, invasion, and migration of OC cells, which could be annulled by silencing of IGF1 or NFKB1. Besides, our in vitro findings were successfully recapitulated in the xenograft mice. These results determined that MAFG-AS1 stimulated the OC malignant progression by upregulating the NFKB1-mediated IGF1 via miR-339-5p, thus highlighting a novel potential therapeutic target against OC.

A Risk Score Model Incorporating Three m6A RNA Methylation Regulators and a Related Network of miRNAs-m6A Regulators-m6A Target Genes to Predict the Prognosis of Patients With Ovarian Cancer.

Ovarian cancer (OC) is the leading cause of cancer-related death among all gynecological tumors. N6-methyladenosine (m6A)-related regulators play essential roles in various tumors, including OC. However, the expression of m6A RNA methylation regulators and the related regulatory network in OC and their correlations with prognosis remain largely unknown. In the current study, we obtained the genome datasets of OC from GDC and GTEx database and analyzed the mRNA levels of 21 key m6A regulators in OC and normal human ovarian tissues. The expression levels of 7 m6A regulators were lower in both the OC tissues and the high-stage group. Notably, the 5-year survival rate of patients with OC presenting low VIRMA expression or high HNRNPA2B1 expression was higher than that of the controls. Next, a risk score model based on the three selected m6A regulators (VIRMA, IGF2BP1, and HNRNPA2B1) was built by performing a LASSO regression analysis, and the moderate accuracy of the risk score model to predict the prognosis of patients with OC was examined by performing ROC curve, nomogram, and univariate and multivariate Cox regression analyses. In addition, a regulatory network of miRNAs-m6A regulators-m6A target genes, including 2 miRNAs, 3 m6A regulators, and 47 mRNAs, was constructed, and one of the pathways, namely, miR-196b-5p-IGF2BP1-PTEN, was initially validated based on bioinformatic analysis and assay verification. These results demonstrated that the risk score model composed of three m6A RNA methylation regulators and the related network of miRNAs-m6A regulators-m6A target genes is valuable for predicting the prognosis of patients with OC, and these molecules may serve as potential biomarkers or therapeutic targets in the future.

Fatty Acid-Binding Protein 4 (FABP4) Suppresses Proliferation and Migration of Endometrial Cancer Cells via PI3K/Akt Pathway.

PURPOSE: Endometrial cancer (EC) is the sixth most common cancer in women and its incidence and mortality have been rising over the last decades. The latest research indicates that FABP4 plays a significant role in multiple types of cancer. But few studies were focused on EC. The aim of this article is to investigate whether FABP4 can suppress tumor growth and metastasis of EC via PI3K/Akt pathway to provide a novel therapeutic target for the treatment of EC. MATERIALS AND METHODS: FABP4 mRNA levels of EC were analysed through The Cancer Genome Atlas database (TCGA), and expression of FABP4 in EC cancer tissues was determined by immunohistochemistry (IHC) assays. Stable overexpressing cell lines were established using lentivirus infection to analyze the biological function of FABP4 in vitro. CCK8 assay and colony formation assay were performed to assess cell proliferation ability. Wound healing assay and transwell were performed to analyse migration and invasion of cells. The subcutaneous xenograft mouse model was used to evaluate tumor growth in vivo. Additionally, all protein levels were detected by Western blotting assay. RESULTS: We found that the expression of the FABP4 mRNA was decreased in tumor samples compared to normal tissue according to TCGA database analysis. Subsequent experimental mRNA and protein expression analysis confirmed that FABP4 expression was lower in EC tissue than normal endometrial tissue. In addition, we found overexpression of FABP4 inhibited the proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Further functional and mechanistic analysis of FABP4 demonstrated that its function is mediated by restraining the phosphorylation of PI3K/Akt signaling pathway. CONCLUSION: Our studies shed light for the first time about the functional role of FABP4 in EC and provide a novel biomarker for EC as well as a therapeutic target for the therapy of EC.