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Metastasis is the main cause of mortality in colorectal cancer (CRC) patients. Exploring the mechanisms of metastasis is of great importance in both clinical and fundamental CRC research. CRC is a highly heterogeneous disease with variable therapeutic outcomes of treatment. In this study, we applied spatial transcriptomics (ST) to generate a tissue-wide transcriptome from two primary colorectal cancer tissues and their matched liver metastatic tissues. Spatial RNA information showed intratumoral heterogeneity (ITH) of both primary and metastatic tissues. The comparison of gene expressions across tissues revealed an apparent enrichment of cancer stem cells (CSCs) in metastatic tissues and identified FOXD1 as a novel metastatic CSC marker. Trajectory and pseudo-time analyses revealed distinct evolutionary trajectories and a dedifferentiation-differentiation process during metastasis. CellphoneDB analysis suggested a dominant interaction of CD74-MIF with tumor cells in metastatic tissues. Further analysis confirmed FOXD1 as a maker of CSCs and the predictor of patient survival, especially in metastatic diseases. Our study found ITH of primary and metastatic tissues and provides novel insights into the cellular mechanisms underlying liver metastasis of CRC and foundations for therapeutic strategies for CRC metastasis.
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Objective: This study aims to explore the association between niacin intake and stroke within a diverse, multi-ethnic population. Methods: A stringent set of inclusion and exclusion criteria led to the enrollment of 39,721 participants from the National Health and Nutrition Examination Survey (NHANES). Two interviews were conducted to recall dietary intake, and the USDA's Food and Nutrient Database for Dietary Studies (FNDDS) was utilized to calculate niacin intake based on dietary recall results. Weighted multivariate logistic regression was employed to examine the correlation between niacin and stroke, with a simultaneous exploration of potential nonlinear relationships using restricted cubic spline (RCS) regression. Results: A comprehensive analysis of baseline data revealed that patients with stroke history had lower niacin intake levels. Both RCS analysis and multivariate logistic regression indicated a negative nonlinear association between niacin intake and stroke. The dose-response relationship exhibited a non-linear pattern within the range of dietary niacin intake. Prior to the inflection point (21.8 mg) in the non-linear correlation between niacin intake and stroke risk, there exists a marked decline in the risk of stroke as niacin intake increases. Following the inflection point, the deceleration in the decreasing trend of stroke risk with increasing niacin intake becomes evident. The inflection points exhibit variations across diverse populations. Conclusion: This investigation establishes a negative nonlinear association between niacin intake and stroke in the broader American population.
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Fish show variation in feeding habits to adapt to complex environments. However, the genetic basis of feeding preference and the corresponding metabolic strategies that differentiate feeding habits remain elusive. Here, by comparing the whole genome of a typical carnivorous fish (Leiocassis longirostris Günther) with that of herbivorous fish, we identify 250 genes through both positive selection and rapid evolution, including taste receptor taste receptor type 1 member 3 (tas1r3) and trypsin We demonstrate that tas1r3 is required for carnivore preference in tas1r3-deficient zebrafish and in a diet-shifted grass carp model. We confirm that trypsin correlates with the metabolic strategies of fish with distinct feeding habits. Furthermore, marked alterations in trypsin activity and metabolic profiles are accompanied by a transition of feeding preference in tas1r3-deficient zebrafish and diet-shifted grass carp. Our results reveal a conserved adaptation between feeding preference and corresponding metabolic strategies in fish, and provide novel insights into the adaptation of feeding habits over the evolution course.
Subject(s)
Genome , Receptors, G-Protein-Coupled , Zebrafish , Animals , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Zebrafish/genetics , Feeding Behavior , Carps/genetics , Carps/metabolism , Food Preferences , Carnivory , Evolution, MolecularABSTRACT
Two enantiomeric pairs of new 3d-4f heterometallic clusters have been synthesized from two enantiomer Schiff base derivatives: (R/S)-2-[(2-hydroxy-1-phenylethylimino)methyl] phenol (R-/S-H2L). The formulae of the series clusters are Co3Ln(R-L)6 (Ln = Dy (1R), Gd (2R)), Co3Ln (S-L)6 (Ln = Dy (1S), Gd (2S)), whose crystal structures and magnetic properties have been characterized. Structural analysis indicated that the above clusters crystallize in the chiral P213 group space. The central lanthanide ion has a coordination geometry of D3 surrounded by three [CoIII(L)2]- anions using six aliphatic oxygen atoms of L2- featuring a star-shaped [CoIII3LnIII] configuration. Magnetic measurements showed the presence of slow magnetic relaxation with an effective energy barrier of 22.33 K in the DyIII derivatives under a zero-dc field. Furthermore, the circular dichroism (CD) spectra of 1R and 1S confirmed their enantiomeric nature.
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Protein tyrosine phosphatase SHP2 activates RAS signaling, which is a novel target for colorectal cancer (CRC) therapy. However, SHP2 inhibitor monotherapy is ineffective for metastatic CRC and a combination therapy is required. In this study, we aimed to improve the antitumor efficacy of SHP2 inhibition and try to explore the resistance mechanism of SHP2 inhibitor. Results showed that WWP1 promoted the proliferation of CRC cells. Genetic or pharmacological inhibition of WWP1 enhanced the effect of SHP2 inhibitor in suppressing tumor growth in vitro and in vivo. WWP1 may mediate feedback reactivation of AKT signaling following SHP2 inhibition. Furthermore, nomogram models constructed with IHC expression of WWP1 and SHP2 greatly improved the accuracy of prognosis prediction for patients with CRC. Our findings indicate that WWP1 inhibitor I3C can synergize with SHP2 inhibitor and is expected to be a new strategy for clinical trials in treating advanced CRC patients.
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Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet persistent challenges such as low response rate and significant heterogeneity necessitate attention. The pivotal role of the major histocompatibility complex (MHC) in ICI efficacy, its intricate impacts and potentials as a prognostic marker, warrants comprehensive exploration. This study integrates single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, and spatial transcriptomic analyses to unveil pan-cancer immune characteristics governed by the MHC transcriptional feature (MHC.sig). Developed through scRNA-seq analysis of 663,760 cells across diverse cohorts and validated in 30 solid cancer types, the MHC.sig demonstrates a robust correlation between immune-related genes and infiltrating immune cells, highlighting its potential as a universal pan-cancer marker for anti-tumor immunity. Screening the MHC.sig for therapeutic targets using CRISPR data identifies potential genes for immune therapy synergy and validates its predictive efficacy for ICIs responsiveness across diverse datasets and cancer types. Finally, analysis of cellular communication patterns reveals interactions between C1QC+macrophages and malignant cells, providing insights into potential therapeutic agents and their sensitivity characteristics. This comprehensive analysis positions the MHC.sig as a promising marker for predicting immune therapy outcomes and guiding combinatorial therapeutic strategies.
Subject(s)
Major Histocompatibility Complex , Neoplasms , Single-Cell Analysis , Humans , Neoplasms/genetics , Neoplasms/immunology , Single-Cell Analysis/methods , Major Histocompatibility Complex/genetics , Major Histocompatibility Complex/immunology , Sequence Analysis, RNA/methods , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , RNA-SeqABSTRACT
Although several previous studies have used resting-state functional magnetic resonance imaging and diffusion tensor imaging to report topological changes in the brain in epilepsy, it remains unclear whether the individual structural covariance network (SCN) changes in epilepsy, especially in pediatric epilepsy with visual cortex resection but with normal functions. Herein, individual SCNs were mapped and analyzed for seven pediatric patients with epilepsy after surgery and 15 age-matched healthy controls. A whole-brain individual SCN was constructed based on an automated anatomical labeling template, and global and nodal network metrics were calculated for statistical analyses. Small-world properties were exhibited by pediatric patients after brain surgery and by healthy controls. After brain surgery, pediatric patients with epilepsy exhibited a higher shortest path length, lower global efficiency, and higher nodal efficiency in the cuneus than those in healthy controls. These results revealed that pediatric epilepsy after brain surgery, even with normal functions, showed altered topological organization of the individual SCNs, which revealed residual network topological abnormalities and may provide initial evidence for the underlying functional impairments in the brain of pediatric patients with epilepsy after surgery that can occur in the future.
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Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid metabolism and protect the liver, but there is limited research on its effects in fish. In the present study, we investigated whether MGF could ameliorate high-starch-induced hepatic damage and lipid accumulation in channel catfish. The channel catfish (Ictalurus punctatus) were fed one of four experimental diets for eight weeks: a control diet (NCD), a high-starch diet (HCD), an HCD supplemented with 100 mg/kg MGF (100 MGF), and an HCD supplemented with 500 mg/kg MGF (500 MGF). The results demonstrated that the weight gain rate (WGR) (p = 0.031), specific growth rate (SGR) (p = 0.039), and feed conversion efficiency (FCE) (p = 0.040) of the 500 MGF group were significantly higher than those of the NCD group. MGF supplementation alleviated liver damage and improved antioxidant capacity (T-AOC) compared to those of the HCD group (p = 0.000). In addition, dietary MGF significantly reduced plasma glucose (GLU) (p = 0.000), triglyceride (TG) (p= 0.001), and low-density lipoprotein cholesterol (LDL) (p = 0.000) levels. It is noteworthy that MGF significantly reduced the plasma total cholesterol (TC) levels (p = 0.000) and liver TC levels (p = 0.005) of channel catfish. Dietary MGF improves cholesterol homeostasis by decreasing the expression of genes that are involved in cholesterol synthesis and transport (hmgcr, sqle, srebf2, sp1, and ldlr) and increasing the expression of genes that are involved in cholesterol catabolism (cyp7a1). Among them, the largest fold decrease in squalene epoxidase (sqle) expression levels was observed in the 100 MGF or 500 MGF groups compared with the HCD group, with a significant decrease of 3.64-fold or 2.20-fold (p = 0.008). And the 100 MGF or 500 MGF group had significantly decreased (by 1.67-fold or 1.94-fold) Sqle protein levels compared to those of the HCD group (p = 0.000). In primary channel catfish hepatocytes, MGF significantly down-regulated the expression of sqle (p = 0.030) and reduced cholesterol levels (p = 0.000). In NCTC 1469 cells, MGF significantly down-regulated the expression of sqle (p = 0.000) and reduced cholesterol levels (p = 0.024). In conclusion, MGF effectively inhibits sqle expression and reduces cholesterol accumulation. The current study shows how MGF supplementation regulates the metabolism and accumulation of cholesterol in channel catfish, providing a theoretical basis for the use of MGF as a dietary supplement in aquaculture.
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Body sizes and head anatomical characteristics play the major role in the head injuries sustained by vulnerable road users (VRU) in traffic accidents. In this study, in order to study the influence mechanism of body sizes and head anatomical characteristics on head injury, we used age, gender, height, and Body Mass Index (BMI) as characteristic parameters to develop the personalized human body multi-rigid body (MB) models and head finite element (FE) models. Next, using simulation calculations, we developed the VRU head injury dataset based on the personalized models. In the dataset, the dependent variables were the degree of head injury and the brain tissue von Mises value, while the independent variables were height, BMI, age, gender, traffic participation status, and vehicle speed. The statistical results of the dataset show that the von Mises value of VRU brain tissue during collision ranges from 4.4 kPa to 46.9 kPa at speeds between 20 and 60 km/h. The effects of anatomical characteristics on head injury include: the risk of a more serious head injury of VRU rises with age; VRU with higher BMIs has less head injury in collision accidents; height has very erratic and nonlinear impacts on the von Mises values of the VRU's brain tissue; and the severity of head injury is not significantly influenced by VRU's gender. Furthermore, we developed the classification prediction models of head injury degree and the regression prediction models of head injury response parameter by applying eight different data mining algorithms to this dataset. The classification prediction models have the best accuracy of 0.89 and the best R2 value of 0.85 for the regression prediction models.
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ABSTRACT: Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal-fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal-fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk. Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.
Subject(s)
Immune Tolerance , Humans , Pregnancy , Female , Immune Tolerance/immunology , Maternal-Fetal Exchange/immunology , Decidua/immunology , Trophoblasts/immunology , Fetus/immunologyABSTRACT
Intensive aquaculture production generates large amounts of sludge. This waste could be considered as a potential source of nutrients that can be recovered and utilized. Little attention has been paid to nutrient recovery from fish sludge. In this study, bioconversion of sludge was evaluated in lab scale under anaerobic (AN), facultative anaerobic (FA) and aerobic (AE) conditions. After 40 days of fermentation, AN recovered the highest values of dissolved total nitrogen (82.7 mg L-1), while AE showed the highest dissolved total phosphorus (11.8 mg L-1) and the highest reduction of total suspended solids (36.0 %). Microbial analysis showed that AN exhibited a distinct bacterial community than that of FA and AE. Furthermore, C. sorokiniana grown in AN effluents collected after 12 days of fermentation achieved the highest biomass production (1.96 g L-1). These results suggest that AN has the best potential to recover nutrients from sludge for production of C. sorokiniana.
Subject(s)
Chlorella , Microalgae , Nitrogen , Nutrients , Phosphorus , Sewage , Chlorella/growth & development , Animals , Fishes , Aquaculture , Waste Disposal, Fluid/methods , Biomass , Anaerobiosis , FermentationABSTRACT
An 88-day feeding trial was conducted to evaluate the effects of dietary inosine 5'-monophosphate (5'-IMP) on the growth performance and salinity and oxidative stress resistance in the juvenile gibel carp CAS III (Carassius auratus gibelio; initial body weight: 7.48 g). Four isonitrogenous and isoenergetic diets containing exogenous 5'-IMP were formulated. P1, P2, P3 and P4 were diets containing 5'-IMP at four concentrations (0, 1, 2 and 4 g kg-1). The four diets were randomly allotted to triplicate tanks in a recirculating system. After the feeding trial, six fish per tank were netted randomly and placed into 12‱ saline water to test their response to salinity stress. The results indicated that the feed conversion rate was enhanced by dietary supplementation with 5'-IMP. The appetite, plasma neuropeptide Y level and feeding rate of the P3 group were lower than those in the control treatment group. Dietary supplementation with 5'-IMP improved the osmoregulatory adaptation of gibel carp under acute salinity stress. Six hours after the salinity stress treatment, in the dietary 5'-IMP treatment group, the plasma cortisol and K+ concentrations were lower and the Na+/K+-ATPase activity was greater than that in the control group. Dietary supplementation with 5'-IMP promoted the expression of the glucocorticoid receptors NKA-α1b and NKCC and retarded the expression of Hsp70 in P4-treated gill filaments and kidneys. Dietary supplementation with 5'-IMP resulted in a stable oxidative-stress-resistant phenotype characterized by increased levels of cellular antioxidants, including SOD, catalase, glutathione peroxidase, glutathione reductase and MPO. The above results of the current study demonstrate that supplementation of 5'-IMP can promote feed utilization and have positive influences on the salinity and oxidative stress resistance of gibel carp.
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The title pyrene-fused spiro-pyran derivative, C30H25NO, crystallizes with two mol-ecules in the asymmetric unit with dihedral angles between their fused-ring sub units of 76.20â (8) and 89.38â (9)°. In the crystal, weak C-Hâ¯π inter-actions link the mol-ecules into a three-dimensional network.
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BACKGROUND: Insulin resistance is associated with chronic complications of diabetes, including diabetic peripheral neuropathy (DPN). Estimated glucose disposal rate (eGDR), calculated by the common available clinical factors, was proved to be an excellent tool to measure insulin resistance in large patient population. Few studies have explored the association between eGDR and DPN longitudinally. Therefore, we performed the current study to analyze whether eGDR could predict the risk of DPN. METHODS: In this prospective study, 366 type 2 diabetes (T2DM) subjects without DPN were enrolled from six communities in Shanghai in 2011-2014 and followed up until 2019-2020. Neuropathy was assessed by Michigan Neuropathy Screening Instrument (MSNI) at baseline and at the end of follow-up. FINDINGS: After 5.91 years, 198 of 366 participants progressed to DPN according to MNSI examination scores. The incidence of DPN in the low baseline eGDR (eGDR < 9.15) group was significantly higher than in the high baseline eGDR (eGDR ≥ 9.15) group (62.37% vs. 45.56%, p = .0013). The incidence of DPN was significantly higher in patients with sustained lower eGDR level (63.69%) compared with those with sustained higher eGDR level (35.80%). Subjects with low baseline eGDR (eGDR < 9.15) had significantly higher risk of DPN at the end of follow-up (odds ratio = 1.75), even after adjusting for other known DPN risk factors. CONCLUSIONS: The 5-year follow-up study highlights the importance of insulin resistance represented by eGDR in the development of DPN in T2DM. Diabetic patients with low eGDR are more prone to DPN and, therefore, require more intensive screening and more attention.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Insulin Resistance , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , Diabetic Neuropathies/etiology , Diabetic Neuropathies/blood , Diabetic Neuropathies/epidemiology , Diabetic Neuropathies/diagnosis , Middle Aged , Female , Male , Follow-Up Studies , Prospective Studies , Blood Glucose/metabolism , Blood Glucose/analysis , Risk Factors , China/epidemiology , Aged , Incidence , Adult , PrognosisABSTRACT
It is difficult to predict the surgical effect and outcome of severe traumatic brain injury (TBI) before surgery. This study aims to approve an evaluation method of computed tomography angiography (CTA) to predict the effect of surgery and outcome in severe TBI. Between January 2010 and January 2020, we retrospectively reviewed 358 severe TBI patients who underwent CTA at admission and reexamination. CTA data were evaluated for the presence of cerebrovascular changes, including cerebrovascular shift (CS), cerebral vasospasm (CVS), large artery occlusion (LAO), and deep venous system occlusion (DVSO). Medical records were reviewed for baseline clinical characteristics and the relationship between CTA changes and outcomes. Cerebrovascular changes were identified in 247 (69.0%) of 358 severe TBI patients; only 25 (10.12%) of them had poor outcomes, and 162 (65.6%) patients had a good recovery. Eighty-three (23.18%) patients were diagnosed with CVS, 10 (12.05%) had a good outcome, 57 (68.67%) had severe disability and 16 (19.28%) had a poor outcome. There were twenty-six (7.3%) patients who had LAO and thirty-one (8.7%) patients who had DVSO; no patients had good recovery regardless of whether they had the operation or not. Cerebrovascular injuries and changes are frequent after severe TBI and correlate closely with prognosis. CTA is an important tool in evaluating the severity, predicting the operation effect and prognosis, and guiding therapy for severe TBI. Well-designed, multicenter, randomized controlled trials are needed to evaluate the value of CTA for severe TBI in the future.
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Brain Injuries, Traumatic , Computed Tomography Angiography , Humans , Brain Injuries, Traumatic/diagnostic imaging , Brain Injuries, Traumatic/surgery , Prognosis , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
Pulmonary fibrosis is a chronic and progressive lung disease with high mortality. This study aims to explore the protective mechanism of quercetin against pulmonary fibrosis regarding cell senescence and gut microbiota. Rats were intratracheally injected with bleomycin (BLM) to establish a pulmonary fibrosis rat model. RLE-6TN cells were stimulated with BLM to build the model of alveolar epithelial cell senescence, and RLE-6TN-derived conditional medium (CM) was harvested to further culture fibroblasts. Histopathological changes were assessed by H&E and Masson staining. α-SMA expression was assessed by immunofluorescence assay. Senescence-associated ß-galactosidase (SA-ß-gal) staining and senescence-associated secretory phenotype (SASP) cytokine assay were conducted to assess cellular senescence. Gut microbiota was analyzed by 16S rRNA gene sequencing. The fibrosis-, senescence-, and PTEN/PI3K/AKT signaling-related proteins were examined by western blot. In BLM-induced pulmonary fibrosis rats, quercetin exerted its protective effects by reducing histological injury and collagen deposition, lessening cellular senescence, and regulating gut microbiota. In BLM-induced alveolar epithelial cell senescence, quercetin inhibited senescence, lessened SASP cytokine secretion of alveolar epithelial cells, and further ameliorated collagen deposition in fibroblasts. In addition, quercetin might exert its functional effects by regulating the PTEN/PI3K/AKT signaling pathway. Moreover, quercetin regulated intestinal dysbacteriosis in BLM-induced pulmonary fibrosis rats, especially boosting the abundance of Akkermansia. To conclude, our findings provide an in-depth understanding of the potential mechanism behind the protective role of quercetin against pulmonary fibrosis.
Subject(s)
Alveolar Epithelial Cells , Bleomycin , Cellular Senescence , Dysbiosis , Gastrointestinal Microbiome , PTEN Phosphohydrolase , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Pulmonary Fibrosis , Quercetin , Signal Transduction , Animals , Quercetin/pharmacology , Cellular Senescence/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/prevention & control , Signal Transduction/drug effects , PTEN Phosphohydrolase/metabolism , Male , Bleomycin/toxicity , Rats , Phosphatidylinositol 3-Kinases/metabolism , Gastrointestinal Microbiome/drug effects , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Rats, Sprague-Dawley , Cell Line , Disease Models, AnimalABSTRACT
Intelligent signal processing in unmanned stores enhances operational efficiency, notably through automated SKUs (Stock Keeping Units) recognition, which expedites customer checkout. Distinguishing itself from generic detection algorithms, the retail product detection algorithm addresses challenges like densely arranged items, varying scales, large quantities, and product similarities. To mitigate these challenges, firstly we propose a novel boundary regression neural network architecture, which enhances the detection of bounding box in dense arrangement, minimizing computational costs and parameter sizes. Secondly, we propose a novel loss function for hierarchical detection, addressing imbalances in positive and negative samples. Thirdly, we enhance the conventional non-maximum suppression (NMS) with weighted non-maximum suppression (WNMS), tying NMS ranking scores to candidate box accuracy. Experimental results on SKU-110K and RPC datasets, two public available databases, show that the proposed SKUs recognition algorithm provides improved reliablity and efficiency over existing methods.
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OBJECTIVE: To explore the DPP4 expression changes and functions in ovarian cancer (OV), as well as the regulation mechanism for DDP4. METHODS: GEPIA2, GSE18520, GSE26712 and UALCAN were used to analyze differences in DPP4 expression between OV tumors and control tissues. Serum DPP4 levels were measured by ELISA. The prognostic values of DPP4 were evaluated using a Kaplan-Meier (KM) plotter. Small interfering RNA was used for DPP4 knockdown in OVCAR-3 and SKOV-3 cells. CCK-8 and scratch healing assays were used to determine the cells' proliferation and migration abilities. Flow cytometry (FCM) was used to detect the cell cycle and apoptosis. A dual-luciferase assay was designed to confirm the regulatory effect of miR-29a-3p on DPP4. RESULTS: The expressions of DPP4 mRNA and protein were decreased in OV tumor tissues. Serum DPP4 levels decreased in OV patients. KM plotter analysis showed correlation between high DPP4 expression and a poor prognosis in OV patients. By targeting knockdown of DPP4, we found that OVCAR-3 and SKOV-3 cells' proliferation was inhibited, while cell's migration ability was significantly promoted. FCM analysis showed that DPP4 knockdown induced a decrease in the S phase. Furthermore, DPP4 was shown to be downregulated by miR-29a-3p and TGFß1 in OVCAR-3 cells, and miR-29a-3p expression was upregulated by TGFß1. The effects of miR-29a-3p and TGFß1 on OVCAR-3 cells' biological behaviors were consistent with DPP4 knockdown. CONCLUSION: DPP4 was downregulated in OV patients. DPP4 knockdown significantly inhibited OVCAR-3 and SKOV-3 cell proliferation and promoted cell migration. DDP4 can be downregulated by TGFß1 through the upregulation of miR-29a-3p in OV cells.
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BACKGROUND: Endometrial proliferative lesions (EPL) usually refer to endometrial hyperplasia (EH) and endometrial cancer (EC). Among patients with premenopausal EPL who wish to preserve their fertility, only those with EH and early-stage EC have the possibility to undergo fertility preservation therapy. However, there is currently a lack of specific and reliable screening criteria and models for identifying these patients. METHODS: This study utilized a retrospective diagnostic study design. The training set included medical record information that met the criteria between August 2017 and October 2022, while the validation set consisted of medical record information that met the criteria from November 2022 to May 2023. The endometrial pathological test served as the gold standard. The serum anti-Mullerian hormone (AMH) level before endometrial sampling and a regression model were employed to predict EPL. RESULTS: The study included a total of 1209 patients with PCOS (1119 in the control group and 90 in the endometrial proliferative lesion group) and 5366 women without PCOS (5249 in the control group and 117 in the proliferative lesion group). In the case of PCOS patients aged 20-39 years, the most effective screening threshold for AMH was found to be a serum AMH level of ≤5.39 ng/mL. The model used for this group was logit(p) = -2.562 - 0.430 × AMH + 0.127 × BMI + 1.512 × hypertension + 0.956 × diabetes -1.145 × regular menstruation. On the other hand, for non-PCOS women aged 20-39 years, the optimal screening threshold for AMH was determined to be a serum AMH value of ≤2.18 ng/mL. The model used for this group was logit(p) = -3.778 - 0.823 × AMH + 0.176 × BMI + 2.660 × diabetes -1.527 × regular menstruation -1.117 × dysmenorrhea. It is important to note that all of these findings have successfully passed internal verification. CONCLUSION: For PCOS and non-PCOS women aged 20-39 years, the serum AMH test and related multiple regression models were obtained for the warning of EPL.
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The main challenges in reconstruction-based anomaly detection include the breakdown of the generalization gap due to improved fitting capabilities and the overfitting problem arising from simulated defects. To overcome this, we propose a new method called PRFF-AD, which utilizes progressive reconstruction and hierarchical feature fusion. It consists of a reconstructive sub-network and a discriminative sub-network. The former achieves anomaly-free reconstruction while maintaining nominal patterns, and the latter locates defects based on pre- and post-reconstruction information. Given defective samples, we find that adopting a progressive reconstruction approach leads to higher-quality reconstructions without compromising the assumption of a generalization gap. Meanwhile, to alleviate the network's overfitting of synthetic defects and address the issue of reconstruction errors, we fuse hierarchical features as guidance for discriminating defects. Moreover, with the help of an attention mechanism, the network achieves higher classification and localization accuracy. In addition, we construct a large dataset for packaging chips, named GTanoIC, with 1750 real non-defective samples and 470 real defective samples, and we provide their pixel-level annotations. Evaluation results demonstrate that our method outperforms other reconstruction-based methods on two challenging datasets: MVTec AD and GTanoIC.