Relationship between sarcopenia and fatty liver in middle-aged and elderly patients with type 2 diabetes mellitus.

OBJECTIVE: In this study, we investigated the relationship between sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with type 2 diabetes mellitus (T2DM) to provide a theoretical foundation for the prevention and treatment of sarcopenia. METHODS: A total of 282 patients diagnosed with T2DM aged 50 and older and were admitted to the Endocrinology Department of Xin Medical University First Affiliated Hospital between December 2021 and February 2023, were selected. Body mass index (BMI), and limb and trunk muscle mass of the patients were measured, and data were collected. Patients were grouped based on the sarcopenia diagnostic criteria. All study participants underwent the same physical examinations and laboratory tests. The relationship between the onset of sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with T2DM was then investigated using statistical analysis. RESULTS: Comparing the sarcopenia group to the non-sarcopenia group revealed statistically significant variations in gender, BMI, fatty liver prevalence rate, uric acid (UA), alanine aminotransferase (ALT), blood glucose, blood lipid associated indicators, and limb skeletal muscle content. There were, however, no statistically significant differences in age, disease duration, hypertension, smoking, or alcohol intake. There was a positive correlation between BMI, UA, fasting c-peptide, and Appendicular Skeletal Muscle Index (ASMI). Higher levels of BMI, ASMI, and UA were identified as protective variables against sarcopenia by multifactorial logistic regression analysis. CONCLUSION: Higher levels of BMI, ASMI, and UA can greatly reduce skeletal muscle atrophy in patients with T2DM. Patients with a fatty liver may be less vulnerable to sarcopenia. There is little evidence, however, that a fatty liver works as a preventive factor against sarcopenia.

Activation of GPR81 by lactate drives tumour-induced cachexia.

Cachexia affects 50-80% of patients with cancer and accounts for 20% of cancer-related death, but the underlying mechanism driving cachexia remains elusive. Here we show that circulating lactate levels positively correlate with the degree of body weight loss in male and female patients suffering from cancer cachexia, as well as in clinically relevant mouse models. Lactate infusion per se is sufficient to trigger a cachectic phenotype in tumour-free mice in a dose-dependent manner. Furthermore, we demonstrate that adipose-specific G-protein-coupled receptor (GPR)81 ablation, similarly to global GPR81 deficiency, ameliorates lactate-induced or tumour-induced adipose and muscle wasting in male mice, revealing adipose GPR81 as the major mediator of the catabolic effects of lactate. Mechanistically, lactate/GPR81-induced cachexia occurs independently of the well-established protein kinase A catabolic pathway, but it is mediated by a signalling cascade sequentially activating Gi-Gßγ-RhoA/ROCK1-p38. These findings highlight the therapeutic potential of targeting GPR81 for the treatment of this life-threatening complication of cancer.

Contrast-enhanced ultrasound for the preoperative prediction of pathological characteristics in breast cancer.

Objective: We aimed to investigate the value of contrast-enhanced ultrasound (CEUS) in the preoperative prediction of the histological grades and molecular subtypes of breast cancer. Methods: A total of 183 patients with pathologically confirmed breast cancer were included. Contrast enhancement patterns and quantitative parameters were compared in different groups. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of CEUS in the preoperative prediction of pathological characteristics, including histologic grade and molecular subtypes. Results: Heterogeneous enhancement, perfusion defects, and peripheral radial vessels were mostly observed in higher histologic grade (grade III) breast cancer. Heterogeneous enhancement and perfusion defect were the most effective indicators for grade III breast cancer, with the areas under the ROC curve of 0.768 and 0.756, respectively. There were significant differences in the enhancement intensity, post-enhanced margin, perfusion defects, and peripheral radial vessel among the different molecular subtypes of breast cancer (all P < 0.01). Perfusion defects and clear edge after enhancement were the best qualitative criteria for the diagnosis of HER-2 overexpressed and triple-negative breast cancers, and the corresponding areas under the ROC curves were 0.804 and 0.905, respectively. There were significant differences in PE, WiR, WiPI, and WiWoAUC between grade III vs grade I and II breast cancer (P < 0.05). PE, WiR, WiPI, and WiWoAUC had good efficiency in the diagnosis of high-histologic-grade breast cancer. PE had the highest diagnostic efficiency in Luminal A, while WiPI had the highest diagnostic efficiency in Luminal B subtype breast cancer, and the areas under the ROC curve were 0.825 and 0.838, respectively. WiWoAUC and WiR were the most accurate parameters for assessing triple-negative subtype breast cancers, and the areas under the curve were 0.932 and 0.922, respectively. Conclusion: Qualitative and quantitative perfusion analysis of contrast-enhanced ultrasound may be useful in the non-invasive prediction of the histological grade and molecular subtypes of breast cancers.

[Blocking Effects of Foliar Conditioners on Cadmium, Arsenic, and Lead Accumulation in Wheat Grain in Compound-contaminated Farmland].

Heavy metal contamination of soil has become a hot issue of social concern due to its impact on the safety of agricultural products in recent years. Wheat is one of the most dominant staple food crops worldwide and has become a major source of toxic metals in human diets. Foliar application was considered to be a more efficient and economical method of heavy metal remediation. Field experiments were carried out in Cd-, As-, and Pb-contaminated farmland soils. The effects of foliar conditioners on the accumulation of Cd, As, and Pb in wheat grains were investigated after being sprayed with Zn (0.2% ZnSO4), Mg (0.4% MgSO4), and Mn (0.2% MnSO4) separately and in combination. Thus, the effective foliar conditioners were selected to block the accumulation of Cd, As, and Pb in wheat grains grown in combined heavy metal-contaminated farmland in north China. The results showed that, compared with that in the control, the Cd, As, and Pb contents in wheat grains of the Zn+Mg+Mn foliar treatment were significantly decreased by 18.96%, 23.87%, and 51.31%, respectively, and TFgrain/straw decreased by 14.62%, 27.73%, and 47.70%, respectively. Thus, spraying the compound foliar conditioner of Zn+Mg+Mn could effectively reduce heavy metal accumulation in wheat grains through inhibition translocation of those metals from stem leaves to grain. In addition, the results indicated that Cd and As were mainly distributed at the central endosperm (34.08%-37.08%), whereas Pb was primarily distributed at the pericarp and seed coat (27.78%) of the wheat grain. Compared with that in the control, spraying the compound foliar conditioner of Zn+Mg+Mn extremely decreased Cd and As accumulation in the aleurone layer of the wheat grain by 81.10% and 82.24%, respectively. Except for the pericarp, seed coat, and central endosperm layers, the Pb content in each grain layer was dramatically decreased by 42.85% to 91.15%. There was only a significant negative correlation between heavy metal content and Zn content in the aleurone layer (P2) of wheat flour. In summary, the accumulation of Cd, As, and Pb in wheat grains, especially in the aleurone layer, could be effectively reduced by foliar conditioner application at the jointing, booting, and early filling stages of wheat, separately. Furthermore, besides the foliar treatment, removing wheat bran to reduce Cd contamination in wheat grains is highly recommended to ensure the safe production of wheat.

Ultrasound contrast-enhanced diagnosis of testicular Leydig cell tumor: A case report and literature review.

Leydig cell tumor (LCT) is a rare testicular tumor. We report a case of an elderly male patient who discovered a left testicular mass during a regular health examination four years ago. The patient did not experience any significant discomfort and opted for regular follow-up visits. During the most recent visit, we performed routine ultrasound and contrast-enhanced ultrasound (CEUS) examinations. By observing the lesion's location, echogenicity, margins, vascular distribution, as well as the rapid enhancement and slow washout characteristics on contrast-enhanced ultrasound, we arrived at a diagnosis of LCT. Subsequently, the patient underwent left inguinal orchiectomy. Postoperative pathology and immunohistochemistry confirmed the diagnosis of LCT. Additionally, we conducted a comprehensive review of LCT-related literature from PubMed and SCOPUS, summarizing the clinical features, follow-up duration, prognosis, and ultrasound characteristics associated with LCT.

Bromine-Enhanced Generation and Epoxidation of Ethylene in Tandem CO2 Electrolysis Towards Ethylene Oxide.

The indirect electro-epoxidation of ethylene (C2 H4 ), produced from CO2 electroreduction (CO2 R), holds immense promise for CO2 upcycling to valuable ethylene oxide (EO). However, this process currently has a mediocre Faradaic efficiency (FE) due to sluggish formation and rapid dissociation of active species, as well as reductive deactivation of Cu-based electrocatalysts during the conversion of C2 H4 to EO and CO2 to C2 H4 , respectively. Herein, we report a bromine-induced dual-enhancement strategy designed to concurrently promote both C2 H4 -to-EO and CO2 -to-C2 H4 conversions, thereby improving EO generation, using single-atom Pt on N-doped CNTs (Pt1 /NCNT) and Br- -bearing porous Cu2 O as anode and cathode electrocatalysts, respectively. Physicochemical characterizations including synchrotron X-ray absorption, operando infrared spectroscopy, and quasi in situ Raman spectroscopy/electron paramagnetic resonance with theoretical calculations reveal that the favorable Br2 /HBrO generation over Pt1 /NCNT with optimal intermediate binding facilitates C2 H4 -to-EO conversion with a high FE of 92.2 %, and concomitantly, the Br- with strong nucleophilicity protects active Cu+ species in Cu2 O effectively for improved CO2 -to-C2 H4 conversion with a FE of 66.9 % at 800 mA cm-2 , superior to those in the traditional chloride-mediated case. Consequently, a single-pass FE as high as 41.1 % for CO2 -to-EO conversion can be achieved in a tandem system.

A medical unsupervised domain adaptation framework based on Fourier transform image translation and multi-model ensemble self-training strategy.

PURPOSE: Well-established segmentation models will suffer performance degradation when deployed on data with heterogeneous features, especially in the field of medical image analysis. Although researchers have proposed many approaches to address this problem in recent years, most of them are feature-adaptation-based adversarial networks, the problems such as training instability often arise in adversarial training. To ameliorate this challenge and improve the robustness of processing data with different distributions, we propose a novel unsupervised domain adaptation framework for cross-domain medical image segmentation. METHODS: In our proposed approach, Fourier transform guided images translation and multi-model ensemble self-training are integrated into a unified framework. First, after Fourier transform, the amplitude spectrum of source image is replaced with that of target image, and reconstructed by the inverse Fourier transform. Second, we augment target dataset with the synthetic cross-domain images, performing supervised learning using the original source set labels while implementing regularization by entropy minimization on predictions of unlabeled target data. We employ several segmentation networks with different hyperparameters simultaneously, pseudo-labels are generated by averaging their outputs and comparing to confidence threshold, and gradually optimize the quality of pseudo-labels through multiple rounds self-training. RESULTS: We employed our framework to two liver CT datasets for bidirectional adaptation experiments. In both experiments, compared to the segmentation network without domain alignment, dice similarity coefficient (DSC) increased by nearly 34% and average symmetric surface distance (ASSD) decreased by about 10. The DSC values were also improved by 10.8% and 6.7%, respectively, compared to the existing model. CONCLUSION: We propose a Fourier transform-based UDA framework, the experimental results and comparisons demonstrate that the proposed method can effectively diminish the performance degradation caused by domain shift and performs best on the cross-domain segmentation tasks. Our proposed multi-model ensemble training strategy can also improve the robustness of the segmentation system.

Upregulation of OTX2-AS1 is Associated With Immune Infiltration and Predicts Prognosis of Gastric Cancer.

BACKGROUND: It is unclear whether the long non-coding RNA (lncRNA) OTX2 antisense RNA 1 (OTX2-AS1) plays a pivotal role in gastric cancer (GC). An analysis of The Cancer Genome Atlas (TCGA) database data and bioinformatics was used to explore the relationship between OTX2-AS1 and GC in the current study. METHODS: We evaluated the relationship between clinical features and OTX2-AS1 expression, prognostic factors, and the significant involvement of OTX2-AS1 in function using various statistical methods, such as Kaplan-Meier method, Cox regression analysis, Gene Set Enrichment Analysis (GSEA), and immune infiltration analysis. GC cell lines were tested for OTX2-AS1 expression using qRT-PCR. RESULTS: A high level of OTX2-AS1 expression was significantly and negatively associated with Helicobacter pylori (H pylori) infection in GC patients (P = .006) and predicted a poorer overall survival (OS) (HR: 1.54; 95% CI: 1.10-2.14; P = .011), progression-free interval (PFI) (HR: 1.75; 95% CI: 1.22-2.51; P = .002) and disease-specific survival (DSS) (HR: 1.85; 95% CI: 1.21-2.85; P = .005) in GC patients. There was an independent correlation between OTX2-AS1 expression (HR: 1.771; 95% CI: 1.164-2.696; P = .008) and OS in patients with GC. There were differential enrichments for the OTX2-AS1 high expression phenotype in the olfactory transduction, G alpha (s) signaling events, keratinization, olfactory signaling pathway, and preimplantation embryo. OTX2-AS1 expression may be related to certain immune-infiltrating cells. Compared to gastric epithelial cells (GES-1), GC cell lines showed a significant increase in OTX2-AS1 expression. CONCLUSION: There was a significant association between OTX2-AS1 expression in GC patients and poor survival, suggesting that it may be a useful biomarker for prognosis and immunotherapy outcome of stomach adenocarcinoma (STAD) in GC.

Analysis of the Mechanism of Action of Kushen in the Treatment of Tuberculosis Based on Network Pharmacology.

Context: Drug-resistant tuberculosis (TB), especially multidrug-resistant TB, has continued to increase and pan-drug-resistant TB and even fully drug-resistant TB have emerged, bringing great challenges to the treatment of TB. Development of new, safe, and effective antituberculosis drugs is an urgent need. Objective: The study intended to evaluate the use of the network pharmacology method to comprehensively and systematically analyze the network relationship of Kushen's main components, targets, and signaling pathways, aiming to provide new ideas and clues for an in-depth study of the mechanism of Kushen's main components in the treatment of pulmonary TB. Design: The research team performed a Network pharmacology analysis. Setting: The study took place in the Department of Respiratory and Critical Care Medicine at the Third People's Hospital of Yichang City in Yichang, Hubei, China. Outcome Measures: The research team: (1) screened Kushen's active ingredients and related targets using the Traditional Chinese Medicine System Pharmacology (TCMSP) database and analysis platform; (2) used the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database to search for disease targets, (3) connected the active ingredient's targets to the disease targets to obtain predictive targets for Kushen to act against TB, (4) used the STRING database to construct a protein-protein interaction (PPI) network map, (5) used the Database for Annotation, Visualization and Integrated Discovery (DAVID) to subject the intersecting genes to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and (6) used the TCMSP and Protein Data Bank (PDB) databases to dock the active ingredients with target-protein molecules. Results: The research team found 45 active ingredients for Kushen and 177 target-protein genes related to active ingredients. The PPI network map of the Kushen-TB targets and found that the top 10 targets of Kushen were: (1) mitogen-activated protein kinase 8 (MAPK8); (2) protein kinase B (AKT1); (3) MAPK1, (4) estrogen receptor 1 (ESR1), (5) rel avian reticuloendotheliosis viral oncogene homolog A (RELA), (6) interleukin-6 (IL6), (7) MYC proto-oncogene, basic helix-loop-helix (bHLH) transcription factor MYC), (8) retinoid X receptor alpha (RXRA), (9) FOS proto-oncogene activator protein 1 (AP-1) transcription factor subunit (FOS), and (10) JUN proto-oncogene AP-1 transcription factor subunit (JUN). The KEGG analysis suggested that Kushen can intervene in TB through the hypoxia-inducible factor 1 (HIF-1) signaling pathway. Conclusions: The network pharmacology analysis showed that Kushen's active ingredients can play a role in the treatment of TB through the HIF-1 signaling pathway.

In vivo growth of subclones derived from Lewis lung carcinoma is determined by the tumor microenvironment.

Heterogeneity is a fundamental feature of human tumors and plays a major role in drug resistance and disease progression. In the present study, we selected single-cell-derived cell lines (SCDCLs) derived from Lewis lung carcinoma (LLC1) cells to investigate tumorigenesis and heterogeneity. SCDCLs were generated using limiting dilution. Five SCDCLs were subcutaneously injected into wild-type C57BL/6N mice; however, they displayed significant differences in tumor growth. Subclone SCC1 grew the fastest in vivo, whereas it grew slower in vitro. The growth pattern of SCC2 was the opposite to that of SCC1. Genetic differences in these two subclones showed marked differences in cell adhesion and proliferation. Pathway enrichment results indicate that signal transduction and immune system responses were the most significantly altered functional categories in SCC2 cells compared to those in SCC1 cells in vitro. The number and activation of CD3+ and CD8+ T cells and NK cells in the tumor tissue of tumor-bearing mice inoculated with SCC2 were significantly higher, whereas those of myeloid cells were significantly lower, than those in the SCC1 and LLC1 groups. Our results suggest that the in vivo growth of two subclones derived from LLC1 was determined by the tumor microenvironment rather than their intrinsic proliferative cell characteristics.

Direct Interaction of Coronavirus Nonstructural Protein 3 with Melanoma Differentiation-Associated Gene 5 Modulates Type I Interferon Response during Coronavirus Infection.

Coronavirus nonstructural protein 3 (nsp3) is a multi-functional protein, playing a critical role in viral replication and in regulating host antiviral innate immunity. In this study, we demonstrate that nsp3 from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and avian coronavirus infectious bronchitis virus (IBV) directly interacts with melanoma differentiation-associated gene 5 (MDA5), rendering an inhibitory effect on the MDA5-mediated type I interferon (IFN) response. By the co-expression of MDA5 with wild-type and truncated nsp3 constructs, at least three interacting regions mapped to the papain-like protease (PLpro) domain and two other domains located at the N- and C-terminal regions were identified in SARS-CoV-2 nsp3. Furthermore, by introducing point mutations to the catalytic triad, the deubiquitylation activity of the PLpro domain from both SARS-CoV-2 and IBV nsp3 was shown to be responsible for the suppression of the MDA5-mediated type I IFN response. It was also demonstrated that both MDA5 and nsp3 were able to interact with ubiquitin and ubiquitinated proteins, contributing to the interaction between the two proteins. This study confirms the antagonistic role of nsp3 in the MDA5-mediated type I IFN signaling, highlighting the complex interaction between a multi-functional viral protein and the innate immune response.

Relationship between bronchopulmonary dysplasia phenotypes with high-resolution computed tomography score in early preterm infants.

Objective: To assess the relationship between high-resolution computed tomography (HRCT) abnormalities and clinical phenotypes of bronchopulmonary dysplasia (BPD). Methods: A retrospective, single-center study was carried out at the Children's Hospital of Fudan University between 2013 and 2020. Preterm infants born at ≤ 32 weeks' gestation who were diagnosed with BPD and had HRCT between 40 and 50 weeks postmenstrual age (PMA)were included in the study. HRCT images from six pulmonary lobes were scored based on seven types of pulmonary lesions from two categories: hyperaeration lesions and parenchymal lesions. The hyperaeration score (HS) included scores of decreased attenuation, mosaic attenuation, and bulla/bleb, while the parenchymal score (PS) included those of linear lesion, consolidation, bronchial wall thickening, and bronchiectasis. All seven scores were summed up to create the total score (TS). One-way ANOVA testing or Kruskal-Wallis testing was adopted for the comparison of HRCT scores with BPD severity and clinical phenotypes. The correlation between HRCT scores and clinical phenotypes was evaluated by Spearman's correlation analysis. Results: A total of 81 cases were included in the study. Cases with more severe BPD had a higher TS (p = 0.01), HS (p = 0.02), PS (p = 0.02), mosaic attenuation score (p = 0.03), bulla/Bleb score (p = 0.03), and linear density score (p = 0.01). TS (r = 0.28), PS (r = 0.35), linear density (r = 0.34), and consolidation (r = 0.24) were correlated with pulmonary hypertension (PH). However, no HRCT score was significantly different between the patients with or without tracheobronchomalacia (TBM). BPD patients with a combination of lung parenchymal disease, PH, and TBM had the highest TS and HS. Conclusion: HRCT scores correlated with BPD severity and PH in our study. HS might be a useful tool in the assessment of BPD severity while linear densities and consolidation might be helpful in predicting PH.

Extracellular Matrix Modulates Outgrowth Dynamics in Ovarian Cancer.

Ovarian carcinoma (OC) forms outgrowths that extend from the outer surface of an afflicted organ into the peritoneum. OC outgrowth formation is poorly understood due to the limited availability of cell culture models examining the behavior of cells that form outgrowths. Prompted by immunochemical evaluation of extracellular matrix (ECM) components in human tissues, laminin and collagen-rich ECM-reconstituted cell culture models amenable to studies of cell clusters that can form outgrowths are developed. It is demonstrated that ECM promotes outgrowth formation in fallopian tube non-ciliated epithelial cells (FNE) expressing mutant p53 and various OC cell lines. Outgrowths are initiated by cells that underwent outward translocation and retained the ability to intercalate into mesothelial cell monolayers. Electron microscopy, optical coherence tomography, and small amplitude oscillatory shear experiments reveal that increased ECM levels led to increased fibrous network thickness and high shear elasticity of the microenvironment. These physical characteristics are associated with outgrowth suppression. The low ECM microenvironment mimicks the viscoelasticity of malignant peritoneal fluid (ascites) and supports cell proliferation, cell translocation, and outgrowth formation. These results highlight the importance of the ECM microenvironment in modulating OC growth and can provide additional insights into the mode of dissemination of primary and recurrent ovarian tumors.

Valeridoids G - Q, Eleven seco-Iridoids from Valeriana jatamansi and Their Bioactivites.

Eleven new seco-iridoids, valeridoids G-Q (1-6 and 8-12), along with four known products, 9-epi-valtral C (7), desacylbaldrinal (13), 11-methoxyviburtinal (14) and baldrinal (15), were obtained from Valeriana jatamansi. Among them, the new compounds were identified by their NMR, HR-ESI-MS spectroscopic data and ECD calculation. Moreover, valeridoid N and O were a pair of C3 epimers, whose ether bonds between C-1 and C-3 opened, and new ether bonds formed between C-3 and C-6. Valeridoid Q belonged to the C-1 degradation of seco-iridoids. As a result, 9-epi-valtral C displayed significant inhibition on Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus argenteus, Shigella flexneri and Klebsiella pneumoniae, and valeridoid Q exhibited the most significant inhibition against Salmonella enteritidis. 9-Epi-valtral C and baldrinal selectively inhibited the growth of human glioma stem cells. Valeridoid Q exhibited significant anti-influenza activity, while valeridoid O inhibited nitric oxide production.

Imaging characteristics of pulmonary BCG/TB infection in patients with chronic granulomatous disease.

In China, tuberculosis (TB) is endemic and the Bacillus Callmette-Güerin (BCG) vaccine is administered to all the newborns, which may lead to BCG infection in patients with chronic granulomatous disease (CGD). Infection of BCG/TB in CGD patients can be fatal and pulmonary is the most affected organ. Our objective was to assess the imaging of pulmonary BCG/TB infection in CGD. We screened 169 CGD patients and identified the patients with pulmonary BCG/TB infection. BCG infection was diagnosis according to the vaccination history, local infection manifestation, acid-fast bacilli staining, specific polymerase chain reaction, and/or spoligotyping. PPD, T-SPOT and acid-fast bacilli staining were used for diagnosis of TB. Totally 58 patients were identified, including TB (n = 7), solely BCG (n = 18), BCG + bacterial (n = 20), and BCG + fungi (n = 13). The onset of BCG disease was much earlier than TB. For those patients only with BCG, lymphadenopathy was the first and most prevalent feature. The most found location was the left axilla, followed by the ipsilateral cervical areas and mediastinal or hilar area. On chest CT, ground-glass opacities, multiple nodules and pulmonary scarring were the most common findings. For TB patients, the pulmonary infections were more serious, including large masses, severe lymphadenopathy, and extensive pulmonary fibrosis. Pulmonary infection of BCG were more common than TB in CGD patients, but much less severe.

The associations between serum high-density lipoprotein cholesterol levels and malignant behavior in pancreatic neuroendocrine neoplasms.

BACKGROUND: The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. METHODS: One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. RESULTS: The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12-0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12-5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02-0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06-0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79-0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70-0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08-0.99). CONCLUSION: Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.

MiR-26a-tetrahedral framework nucleic acids mediated osteogenesis of adipose-derived mesenchymal stem cells.

OBJECTIVES: Delivery systems that provide time and space control have a good application prospect in tissue regeneration applications, as they can effectively improve the process of wound healing and tissue repair. In our experiments, we constructed a novel micro-RNA delivery system by linking framework nucleic acid nanomaterials to micro-RNAs to promote osteogenic differentiation of mesenchymal stem cells. MATERIALS AND METHODS: To verify the successful preparation of tFNAs-miR-26a, the size of tFNAs-miR-26a were observed by non-denaturing polyacrylamide gel electrophoresis and dynamic light scattering techniques. The expression of osteogenic differentiation-related genes and proteins was investigated by confocal microscope, PCR and western blot to detect the impact of tFNAs-miR-26a on ADSCs. And finally, Wnt/ß-catenin signaling pathway related proteins and genes were detected by confocal microscope, PCR and western blot to study the relevant mechanism. RESULTS: By adding this novel complex, the osteogenic differentiation ability of mesenchymal stem cells was significantly improved, and the expression of alkaline phosphatase (ALP) on the surface of the cell membrane and the formation of calcium nodules in mesenchymal stem cells were significantly increased on days 7 and 14 of induction of osteogenic differentiation, respectively. Gene and protein expression levels of ALP (an early marker associated with osteogenic differentiation), RUNX2 (a metaphase marker), and OPN (a late marker) were significantly increased. We also studied the relevant mechanism of action and found that the novel nucleic acid complex promoted osteogenic differentiation of mesenchymal stem cells by activating the canonical Wnt signaling pathway. CONCLUSIONS: This study may provide a new research direction for the application of novel nucleic acid nanomaterials in bone tissue regeneration.

Disentangled representation and cross-modality image translation based unsupervised domain adaptation method for abdominal organ segmentation.

PURPOSE: Existing medical image segmentation models tend to achieve satisfactory performance when the training and test data are drawn from the same distribution, while they often produce significant performance degradation when used for the evaluation of cross-modality data. To facilitate the deployment of deep learning models in real-world medical scenarios and to mitigate the performance degradation caused by domain shift, we propose an unsupervised cross-modality segmentation framework based on representation disentanglement and image-to-image translation. METHODS: Our approach is based on a multimodal image translation framework, which assumes that the latent space of images can be decomposed into a content space and a style space. First, image representations are decomposed into the content and style codes by the encoders and recombined to generate cross-modality images. Second, we propose content and style reconstruction losses to preserve consistent semantic information from original images and construct content discriminators to match the content distributions between source and target domains. Synthetic images with target domain style and source domain anatomical structures are then utilized for training of the segmentation model. RESULTS: We applied our framework to the bidirectional adaptation experiments on MRI and CT images of abdominal organs. Compared to the case without adaptation, the Dice similarity coefficient (DSC) increased by almost 30 and 25% and average symmetric surface distance (ASSD) dropped by 13.3 and 12.2, respectively. CONCLUSION: The proposed unsupervised domain adaptation framework can effectively improve the performance of cross-modality segmentation, and minimize the negative impact of domain shift. Furthermore, the translated image retains semantic information and anatomical structure. Our method significantly outperforms several competing methods.

LncRNA HCG11 promotes 5-FU resistance of colon cancer cells through reprogramming glucose metabolism by targeting the miR-144-3p-PDK4 axis.

BACKGROUND: Colorectal cancer (CRC), one of the most common human malignancies, is a leading cause of the cancer-related mortality. 5-FU is a first-line chemotherapeutic agent against CRC. Although CRC patients responded to 5-FU therapy initially, a part of patients succumbed to CRC due to the acquired drug resistance. Thus, investigating molecular mechanisms underlying chemoresistance will contribute to developing novel strategies against colorectal cancer. OBJECTIVE: Accumulation evidence revealed pivotal roles of long non-coding RNAs (lncRNAs) in tumorigenesis and chemoresistance of CRC. However, the precise roles and molecular mechanisms of lncRNA-HCG11 in CRC remain unclear. This study aimed to investigate the biological roles and underlying mechanisms of HCG11 as well as its molecular targets in regulating the cellular metabolism processes, which facilitate the chemoresistance of CRC. METHODS AND RESULTS: This study uncovers that HCG11 was significantly upregulated in CRC tumors tissues and cell lines. Moreover, HCG11 was elevated in 5-FU resistant CRC tumors. Silencing HCG11 inhibited colon cancer cell proliferation, migration, invasion and glucose metabolism and sensitized CRC cells to 5-FU. In addition, we detected increased HCG11 expression level and glucose metabolism in the established 5-FU resistant CRC cell line (DLD-1 5-FU Res). Furthermore, microRNA-microArray, RNA pull-down and luciferase assays demonstrated that HCG11 inhibited miR-144-3p which displays suppressive roles in colon cancer via sponging it to form a ceRNA network. We identified pyruvate dehydrogenase kinase 4 (PDK4), which is a glucose metabolism key enzyme, was directly targeted by miR-144-3p in CRC cells. Rescue studies validated that the miR-144-3p-inhibited glucose metabolism and 5-FU sensitization were through targeting PDK4. Finally, restoration of miR-144-3p in HCG11-overexpressing DLD-1 5-FU resistant cells successfully overcame the HCG11-faciliated 5-FU resistance via targeting PDK4. CONCLUSION: In summary, this study reveals critical roles and molecular mechanisms of the HCG11-mediated 5-FU resistance through modulating the miR-144-3p-PDK4-glucose metabolism pathway in CRC.