Development of Preladenant-Based Radiotracers for Imaging A2AR in Tumors.

Activation of the adenosine 2A receptor (A2AR) can lead to tumor immunosuppression, which results in poor prognosis of immunotherapy. The aim of this study was to design novel 18F-labeled probes ([18F]F-PFP2 and [18F]F-PFP4) to visualize A2AR in the tumor. The uptake of radioprobes in A2AR-negative 4T1 breast tumor was lower than that of A2AR-positive B16F10 melanoma at 1 h p.i. (1.22 ± 0.36% ID/g vs 2.80 ± 0.72% ID/g), 2 h p.i. (1.09 ± 0.20% ID/g vs 2.93 ± 0.76% ID/g) and 3 h p.i. (0.89 ± 0.27% ID/g vs 2.73 ± 0.58% ID/g), respectively. B16F10 lung metastasis models were employed to expand the application scenarios, observing significantly higher uptake of [18F]F-PFP2 in metastatic lesions compared to normal lung tissue (5.55 ± 2.18% ID/g vs 1.89 ± 0.65% ID/g, tumor/lung ratio ∼3). It is given that [18F]F-PFP2 might lay the foundation for establishing an A2AR-targeted imaging evaluation system for tumors, which will provide more precise guidance for personalized treatment.

Effects of White Noise on Pain Scores and Salivary Cortisol Levels in Surgical Neonates: A Randomized Controlled Trial.

BACKGROUND: Neonates experience varying intensities of pain after surgery. While white noise has been used for postoperative pain relief in infants, its effects on neonates after surgery need further exploration. PURPOSE: This study aimed to evaluate the effects of white noise on pain scores and salivary cortisol levels in surgical neonates. METHODS: In this randomized controlled trial, 64 neonates scheduled for surgery were recruited and assigned by block randomization into 2 groups. The intervention group listened to white noise at 50 dB, while the control group listened to white noise at 0 dB, for 30 minutes 6 times for 48 hours postoperatively. Pain scores, measured by the COMFORTneo Scale, and salivary cortisol levels were compared. RESULTS: Although pain scores decreased after surgery in all subjects, no statistically significant difference was observed between the 2 groups (P = .937). There was a significant difference between pre- and postintervention pain scores in the intervention group only (P = .006). Salivary cortisol levels decreased after intervention in the intervention group, but there was no significant difference between pre- and postintervention levels in the 2 groups (P = .716). IMPLICATIONS FOR PRACTICE: Given the reduction in pain scores and salivary cortisol concentrations after white noise intervention, white noise shows potential as an adjunctive soothing measure for neonates after surgery. IMPLICATIONS FOR RESEARCH: Future studies are needed to confirm the efficacy and utility of white noise intervention in clinical settings.

Rational Design and Pharmacomodulation of 18F-Labeled Biotin/FAPI-Conjugated Heterodimers.

Due to the complex heterogeneity in different cancer types, the heterodimeric strategy has been intensively practiced to improve the effectiveness of tumor diagnostics. In this study, we developed a series of novel 18F-labeled biotin/FAPI-conjugated heterobivalent radioligands ([18F]AlF-NSFB, [18F]AlF-NSFBP2, and [18F]AlF-NSFBP4), synergistically targeting both fibroblast activation protein (FAP) and biotin receptor (BR), to enhance specific tumor uptake and retention. The in vitro and in vivo biological properties of these dual-targeting tracers were evaluated, with a particular focus on positron emission tomography imaging in A549 and HT1080-FAP tumor-bearing mice. Notably, in comparison to the corresponding FAP-targeted monomer [18F]AlF-NSF, biotin/FAPI-conjugated heterodimers exhibited a high uptake in tumor and prolong retention. In conclusion, as a proof-of-concept study, the findings validated the superiority of biotin/FAPI-conjugated heterodimers and the positive influence of biotin and linker on pharmacokinetics of radioligands. Within them, the bispecific [18F]AlF-NSFBP4 holds significant promise as a candidate for further clinical translational studies.

Urinary peptidome analysis in CKD and IgA nephropathy.

Background: Chronic kidney disease (CKD) has emerged as a significant challenge to human health and economic stability in aging societies worldwide. Current clinical practice strategies remain insufficient for the early identification of kidney dysfunction, and the differential diagnosis of immunoglobulin A nephropathy (IgAN) predominantly relies on invasive kidney biopsy procedures. Methods: First, we assessed a case-control cohort to obtain urine samples from healthy controls and biopsy-confirmed CKD patients. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) was applied to detect urinary peptide and then these urinary peptide profiles were used to construct diagnostic models to distinguish CKD patients from controls and identify IgAN patients from other nephropathy patients. Furthermore, we assessed the robustness of the diagnostic models and their reproducibility by applying different algorithms. Results: A rapid and accurate working platform for detecting CKD and its IgAN subtype based on urinary peptide pattern detected by MALDI-TOF MS was established. Naturally occurring urinary peptide profiles were used to construct a diagnostic model to distinguish CKD patients from controls and identify IgAN patients from other nephropathy patients. The performance of several algorithms was assessed and demonstrated that the robustness of the diagnostic models as well as their reproducibility were satisfactory. Conclusions: The present findings suggest that the CKD-related and IgAN-specific urinary peptides discovered facilitate precise identification of CKD and its IgAN subtype, offering a dependable framework for screening conditions linked to renal dysfunction. This will aid in comprehending the pathogenesis of nephropathy and identifying potential protein targets for the clinical management of nephropathy.

Lymph node metastasis related gene BICC1 promotes tumor progression by promoting EMT and immune infiltration in pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is one of the most aggressive abdominal malignancies with a poor prognosis and it is urgent to find effective biomarkers for prediction. Although BICC1 expression is related to the survival, no evidence for its role in PC development has been found. METHODS: We used RNA-seq data to screen for molecular markers highly associated with lymph node metastasis. The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) public databases were used to analyze the expression and prognosis of Differential Expressed Genes (DEGs) in PC. R studio was used for visualization and functional analysis. RESULTS: BicC Family RNA Binding Protein 1 (BICC1) was a lymph node metastasis-related DEGs in PC patients. Our study found that BICC1 mRNA levels in the tumor tissue were significantly higher and associated with poorer prognosis. Enrichment analysis found that BICC1 was enriched primarily in the Epithelial Mesenchymal Transition (EMT) pathway. Using the ESTIMATE and CIBERSORT algorithms, we found that BICC1 was related to immune cell infiltration. As a regulator of multiple immune checkpoints, BICC1 was also involved in PC's immune response. CONCLUSIONS: BICC1 has the potential to be a new marker in association with lymph node metastasis as well as immune infiltration of PC. In addition to being a prognostic indicator, it may also be a potential therapeutic target.

NEDD4L inhibits migration, invasion, cisplatin resistance and promotes apoptosis of bladder cancer cells by inactivating the p62/Keap1/Nrf2 pathway.

PURPOSE: This study identified the function of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) on bladder cancer (BLCA). METHODS: NEDD4L expression in BLCA patients was scrutinized. The function of NEDD4L on the viability, apoptosis, migration and invasion of BLCA cells was evaluated by cell counting kit-8, flow cytometry and Transwell assays. The effect of NEDD4L on the cisplatin (DDP) resistance of the DDP-resistant BLCA cells was explored. The influence of NEDD4L on the p62/Keap1/Nrf2 pathway activity in BLCA cells was tested by Western blot. Rescue experiments were implemented to verify whether NEDD4L regulated BLCA cell malignant behavior by mediating the Keap1/Nrf2 pathway activity via p62. The effect of NEDD4L on the growth and the p62/Keap1/Nrf2 pathway activity in vivo was researched in xenograft tumor nude mice models. RESULTS: The down-regulated NEDD4L in BLCA patients was associated with unfavorable survival. NEDD4L suppressed the viability (inhibition rate 57.1%/49.0%), migration (inhibition rate 49.7%/77.1%), invasion (inhibition rate 50.6%/75.7%), promoted the apoptosis of T24/5637 cells (promotion rate 243.8%/201.9%), reduced IC 50 of DDP-resistant T24/5637 cells from 132.2/101.8 to 57.81/59.71 µM, respectively, and inactivated the p62/Keap1/Nrf2 pathway in T24/5637 cells. p62 up-regulation partially abrogated the inhibition of NEDD4L on the Keap1/Nrf2 pathway activity, the malignant behavior of BLCA cells, and the DDP resistance of DDP-resistant BLCA cells. NEDD4L overexpression inhibited the tumor growth and the p62/Keap1/Nrf2 pathway activity in vivo in BLCA. CONCLUSION: NEDD4L inhibits the progression of BLCA by inactivating the p62/Keap1/Nrf2 pathway. It may be an effective target for BLCA treatment.

Boosting Anti-tumour Immunity Using Adjuvant Apigenin.

The interactions and secretions within the tumour have a pivotal role in tumour growth and therapy. Immunosuppressive cells such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumour-associated macrophages (TAMs), and cancer-associated fibroblasts (CAFs) secrete some substances, which can result in the exhaustion of anti-tumour immunity. To stimulate anti-tumour immunity, suppression of the secretion and interactions of immunosuppressive cells, on the other hand, stimulation of proliferation and activation of natural killer (NK) cells and CD8+ T lymphocytes are required. Apigenin is a flavone with anticancer properties. Emerging evidence shows that not only does apigenin modulate cell death pathways in cancer cells but it also can stimulate anti-tumour immune cells to release death signals and suppress the release of tumour-promoting molecules. In this review, we discuss the interactions between apigenin and various cells within the tumour microenvironment (TME). These interactions may enhance anti-tumour immunity to improve the efficiency of anticancer remedies such as immunotherapy.

Effects of Holliday Junction-Recognition Protein-Mediated C-Jun N-Terminal Kinase/ Signal Transducer and Activator of Transcription 3 Signaling Pathway on Cell Proliferation, Cell Cycle and Cell Apoptosis in Bladder Urothelial Carcinoma.

The Holliday Junction-Recognition Protein (HJURP) was upregulated in several tumors, which was associated with poor outcome. This study investigated the effects of the HJURP-mediated c-Jun N-terminal kinase (JNK)/ signal transducer and activator of transcription 3 (STAT3) pathway on bladder urothelial carcinoma (BLUC). Online databases were used to analyze HJURP expression in BLUC and the correlation of HJURP to JNK1 [mitogen-activated protein kinase 8 (MAPK8)], JNK2 (MAPK9), STAT3, marker of proliferation Ki-67 (MKI67), proliferating cell nuclear antigen (PCNA), cyclin dependent kinase 2 (CDK2), CDK4 and CDK6. HJURP expression was detected in BLUC cells and human normal primary bladder epithelial cells (BdECs). BLUC cells were treated with HJURP lentivirus activation /shRNA lentivirus particles or JNK inhibitor SP600125. HJURP was upregulated in BLUC tissues and correlated with poor prognosis of patients (all P < 0.05). HJURP in tumor positively correlated with MAPK8 (R = 0.30), MAPK9 (R = 0.30), STAT3 (R = 0.15), MKI67 (R = 0.60), PCNA (R = 0.46), CDK2 (R = 0.39), CDK4 (R = 0.24) and CDK6 (R = 0.21). The JNK inhibitor SP600125 decreased p-JNK/JNK and p-STAT3/STAT3 in BLUC cells, which was reversed by HJURP overexpression (P < 0.05). The HJURP-mediated JNK/STAT3 pathway promoted BLUC cell proliferation and inhibited cell apoptosis (P < 0.05). HJURP reversed the arrested G0/G1 phase of BLUC cells by SP600125. HJURP acted as an oncogene to regulate BLUC cell proliferation, apoptosis and the cell cycle by mediating the JNK/STAT3 pathway. Therefore, HJURP targeting might be an attractive novel therapeutic target for early diagnosis and treatment in BLUC.

Circular RNA KIF4A Promotes Liver Metastasis of Breast Cancer by Reprogramming Glucose Metabolism.

Background: Circular RNAs (circRNAs) regulate complex functional processes and play crucial roles in cancer development and progression. It was reported that circKIF4 regulates the progression of triple-negative breast cancer (TNBC). This study evaluates the role of circKIF4 in breast cancer distant metastasis and metabolic reprogramming. Methods: RT-qPCR was performed to verify the expression of circKIF4A in breast cancer, liver metastatic tissues, and cell lines. The function of circKIF4A in metastasis was evaluated both in vitro and in vivo through a series of experiments, including cell migration and glucose intake experiments. Additionally, we conducted molecular experiments to clarify the regulatory role of circKIF4A. We then conducted a Luciferase reporter assay and an RNA immunoprecipitation assay to identify the molecular interactions between circKIF4A and miRNA. Results: circKIF4A was overexpressed in breast cancer cell lines and tissues, inhibiting its expression and suppressing breast cancer growth and metastasis. Interestingly, we observed that circKIF4A reprogrammed the glucose metabolism of breast cancer, and silencing circKIF4A greatly affected glucose uptake and lactate production in breast cancer cells. miR-335 can be sponged by circKIF4A, which affected the expression of ALDOA/OCT4 protein and regulated HK2/PKM2 expression. Conclusions: This study demonstrated that the circKIF4A-miR-335-OCT4/ALDOA-HK2/PKM2 axis is critical to breast cancer metabolic reprogramming, indicating that this axis could be a novel therapeutic target for the treatment of liver metastasis of breast cancer.

Multi-tissue metabolomic profiling reveals potential mechanisms of cocoon yield in silkworms (Bombyx mori) fed formula feed versus mulberry leaves.

Use of formula feed (FF) for silkworms for all instars, has promoted transformation and progress in traditional sericulture. However, the cocoon yield of FF silkworms has failed to reach that of silkworms fed mulberry leaves (ML). The biological mechanisms underlying this phenomenon have not been well described. This study aimed to identify metabolic mechanisms and potential biomarkers relating to the poor cocoon yield of FF silkworms. In this study, silkworms received treatments of either ML (ML group) or FF (FF group) for all instars. At the 3rd day of the 5th instar, the midgut (MG), hemolymph (HL) and posterior silk gland (PSG) were collected for the metabolome profiles detection. The remaining silkworms were fed ML or FF until cocooning for investigation. The whole cocoon yield (WCY) was significantly higher in the FF group than the ML group (p < 0.05), whereas the cocoon shell weight (CSW) and cocoon shell rate (CSR) were significantly lower in the FF group (p < 0.05). A total of 845, 867 and 831 metabolites were qualified and quantified in the MG, HL and PSG of the FF silkworms, respectively. Correspondingly, 789, 833 and 730 metabolites were quantified in above three tissues of the ML group. Further, 230, 249 and 304 significantly different metabolites (SDMs) were identified in the MG, HL and PSG between the FF and ML group, respectively. Eleven metabolic pathways enriched by the SDMs were mutual among the three tissues. Among them, cysteine and methionine metabolism, arginine biosynthesis, and arginine and proline metabolism were the top three pathways with the highest impact value in the PSG. Six biomarkers were obtained through biomarker analysis and Pearson correlation calculation. Among them, homocitrulline, glycitein, valyl-threonine, propyl gallate and 3-amino-2,3-dihydrobenzoic acid were positively correlated with WCY, but negatively correlated with CSW and CSR (p < 0.05). An opposite correlation pattern was observed between 3-dimethylallyl-4-hydroxyphenylpyruvate and the three cocoon performance traits. Overall, three key metabolic pathways and six biomarkers associated with cocoon yield were interpreted, and should provide directions for formula feed optimization in factory-raised silkworms.

Analysis of diagnostic characteristics and clinical related factors of 70 patients with atelectasis by painless bronchoscopy.

Objectives: To analyze the diagnostic characteristics and clinical related factors of patients with atelectasis by painless electronic bronchoscopy. Methods: A retrospective analysis was performed on 70 patients with atelectasis admitted to Xuancheng People's Hospital from April 2019 to June 2021. The clinical data of the patients and the diagnosis characteristics under painless electronic bronchoscope were analyzed, and the clinical related factors were investigated. Results: Seventy patients with atelectasis underwent pathological examination and bacteriological examination after painless electronic bronchoscopy, including 16 cases (22.86%) of inflammation, 11 cases (15.71%) of tuberculosis, 36 cases (51.43%) of tumor, one case (1.43%) of inflammatory polyp, one case (1.43%) of congenital dysplasia, two cases (2.86%) of foreign body inhalation, and three cases (4.29%) of other symptoms. Male patients with atelectasis showed most cauliflower-like tumors and mucosal swelling under electronic bronchoscopy (P<0.05), while female patients showed scar occlusion/stenosis at most (P<0.05). Middle-aged and elderly patients under electronic bronchoscopy showed most cauliflower-like tumors, scar stenosis/occlusion and mucosal swelling cavity, while young patients mainly showed necrosis and purulent secretions. Heavy smokers were most likely to have cauliflower-like tumors, while non-smokers were predominantly with scar stenosis/occlusion. Conclusions: Painless electronic bronchoscopy is of great value in the clinical diagnosis of patients with atelectasis, and it is likely to further clarify the etiology of atelectasis. Age, sex, and quantity of smoking may be clinical factors associated with atelectasis.

Sensitivity of PCR analysis (melting curve method) in diagnosis of Pulmonary Tuberculosis (PTB) based on Bronchoalveolar Lavage (BAL) by bronchoscope.

Objectives: To evaluate the sensitivity of the real-time PCR assay melting curve method in the diagnosis of pulmonary tuberculosis (PTB) by analyzing bronchoalveolar lavage fluid (BALF) obtained from bronchoscopy. Methods: A total of 214 PTB patients who were treated at Xuancheng People's Hospital respiratory and infection department during January 2018 to January 2021 were included in this study. Bronchoscopic bronchoalveolar lavage fluid (BALF) examined by polymerase chain reaction (melting curve method), BALF smear, BALF culture, lipoarabinomannan (LAM) antigen test for diagnosis of tuberculosis (TB) (LAM-TB), acid-fast stain (AFS), and serum adenosine deaminase (ADA) test were conducted respectively to compare their positive predictive values (PPVs). Results: Of the 214 patients with confirmed PTB, 84.11% were BALF melting curve method positive, significantly higher than the positive results yielded by other PTB screening tests, i.e., LAM-TB (69.16%), AFS (51.87%), ADA (49.07%), BALF culture (62.15%), and BALF smear (41.12%) (p<0.05, respectively). The PPVs were increased to 92.06%, 93.93%, 92.99%, 95.79%, and 91.12% when BALF melting curve method was performed in combination with LAM-TB, AFS, ADA, BALF culture, and BALF smear, respectively, significantly higher than that produced by BALF melting curve method or the combined use of any two of the non-BALF melting curve method tests (p<0.05, respectively). Conclusion: BALF melting curve method is an ideal diagnostic approach to PTB, which is of a higher diagnostic value compared with LAM-TB, AFS, ADA, BALF culture, and BALF smear.

Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model.

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate ( Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.

Nobiletin as an inducer of programmed cell death in cancer: a review.

Cancer resistance to therapy is a big issue in cancer therapy. Tumours may develop some mechanisms to reduce the induction of cell death, thus stimulating tumour growth. Cancer cells may show a low expression and activity of tumour suppressor genes and a low response to anti-tumour immunity. These mutations can increase the resistance of cancer cells to programmed cell death mechanisms such as apoptosis, ferroptosis, pyroptosis, autophagic cell death, and some others. The upregulation of some mediators and transcription factors such as Akt, nuclear factor of κB, signal transducer and activator of transcription 3, Bcl-2, and others can inhibit cell death in cancer cells. Using adjuvants to induce the killing of cancer cells is an interesting strategy in cancer therapy. Nobiletin (NOB) is a herbal-derived agent with fascinating anti-cancer properties. It has been shown to induce the generation of endogenous ROS by cancer cells, leading to damage to critical macromolecules and finally cell death. NOB may induce the activity of p53 and pro-apoptosis mediators, and also inhibit the expression and nuclear translocation of anti-apoptosis mediators. In addition, NOB may induce cancer cell killing by modulating other mechanisms that are involved in programmed cell death mechanisms. This review aims to discuss the cellular and molecular mechanisms of the programmed cell death in cancer by NOB via modulating different types of cell death in cancer.

ROC1 promotes the malignant progression of bladder cancer by regulating p-IκBα/NF-κB signaling.

BACKGROUND: Regulator of cullins 1 (ROC1) is an important catalytic subunit of cullin-RING E3 ligase. Nuclear factor-kappa B (NF-κB) signaling is closely related to tumor invasion and metastasis. Earlier, we reported that ROC1 was associated with a poor prognosis in patients with bladder cancer (BCa). However, it is unclear whether ROC1 is involved in the NF-κB signaling associated with malignant BCa progression. METHODS: The expression of ROC1 and p65 in bladder cancer and paracancerous tissues were detected by immunohistochemistry (IHC). Pearson correlation was used to assess correlation between ROC1 and p65 protein expressions. The wound-healing and transwell assays were used to monitor cell invasion and migration. The effect of ROC1 on the expression of key proteins in the NF-κB signaling was determined by immunofluorescence and western blot (WB). Cycloheximide (CHX), MG132 and immunoprecipitation assays were used to evaluate the effect of ROC1 on the ubiquitination of phosphorylated inhibitor of kappa B alpha (p-IκBα). A lung metastasis mouse model was generated to detect the role of ROC1 in tumor metastasis. RESULTS: We found that ROC1 was up-regulated in BCa tissues and cell lines, and high ROC1 levels were positively correlated with higher tumour grade, lymph node metastasis, distant metastasis and poor prognosis. Linear-regression analysis showed significant a Pearson correlation between ROC1 and nuclear p65 expression in BCa tissue microarray (TMA) samples. Functional studies demonstrated that ROC1 promoted BCa cell invasion and migration. In vitro and in vivo experiments showed that ROC1 activated NF-κB signaling by enhancing the ubiquitination of p-IκBα, which caused p65 nuclear translocation and promoted the transcription of some metastasis-related target genes, such as urokinase-type plasminogen activator receptor (uPAR), intracellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and matrix metalloproteinase 9 (MMP9), resulting in promoting BCa metastasis. CONCLUSION: ROC1 plays an important role in the progression of BCa and serves as a potential diagnostic and therapeutic target for patients with BCa.

LncRNA NEAT1 Knockdown Inhibits Retinoblastoma Progression by miR-3619-5p/LASP1 Axis.

Retinoblastoma (RB) is the most common intraocular tumor in childhood. Long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NTAT1) has been reported to be related to RB progression. This study aims to study the molecular mechanism of NEAT1 in regulating cell cycle, proliferation, apoptosis, migration, and invasion in RB. The expression levels of NEAT1 and miR-3619-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of LIM and SH3 domain protein 1 (LASP1) was measured by western blot. The proliferation of RB cells was analyzed by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were evaluated by transwell assay. Cell cycle and apoptosis were assessed by flow cytometry analysis. The association between miR-3619-5p and NEAT1 or LASP1 was predicted by starBase 3.0 database and identified by dual-luciferase reporter assay. The effects of NEAT1 knockdown on the tumor growth in vivo were detected by in vivo tumor formation assay. NEAT1 expression was dramatically up-regulated, and miR-3619-5p expression was obviously downregulated in RB tissues and cells compared with control groups. The protein level of LASP1 was obviously increased in RB tissues or cells relative to paracancerous normal tissues or cells, respectively. Functionally, NEAT1 silencing inhibited RB cell migration, invasion, and proliferation, whereas induced cell apoptosis and cell cycle arrest in RB; this phenomenon was partially abolished by miR-3619-5p inhibitor. Mechanistically, NEAT1 acted as a sponge of miR-3619-5p, and miR-3619-5p was associated with LASP1. In addition, NEAT1 knockdown decreased the volume and weight of RB tumor in vivo. Together, NEAT1 silencing repressed cell migration, invasion, and proliferation, whereas induced cell apoptosis and cycle arrest by sponging miR-3619-5p to inhibit LASP1 expression in RB cells. This study may provide a theoretical basis for RB therapy.

Retinal vascular abnormalities and their associations with cardiovascular and cerebrovascular diseases: a Study in rural southwestern Harbin, China.

BACKGROUND: Limited data is available on retinal vessel morphology in the north China. The study aimed to evaluate the prevalence of retinal vascular abnormalities (RVAs) and investigate their associations with the self-reported diagnosis of cardiovascular and cerebrovascsular diseases (CCVds) in a rural adult population of northeast China. METHODS: A population-based, cross-sectional study was conducted, using the cluster random sampling method. One eye of each participant was photographed with a non-mydriatic fundus camera. RVAs including focal and general arteriolar narrowing (FAN and GAN), arteriovenous nicking (AVN), arteriolar sheathing (AS), and retinopathy were evaluated. Data on self-reported diagnosis of cardiovascular and cerebrovascular diseases and status of smoking and alcohol drinking were obtained from questionnaires. RESULTS: Among the 6267 participants with an age ≥ 50 years, photographs were obtained of 99.2%, with quality sufficient to perform retinal evaluations in 82.5%. The prevalence of FAN, AVN, AS, retinopathy and GAN were 9.1, 8.9, 5.0, 6.6 and 6.2%, respectively. All the retinal lesions were associated with hypertension (all P < 0.01). After adjusting for age, gender, and left/right eyes, hypertension, hyperlipidaemia, diabetes mellitus, habits of past or current smoking and alcohol consumption, AVN was strongly associated with the self-reported diagnosis histories of coronary heart diseases(CHD) (OR, 1.44; 95% CI, 1.09, 1.89) and retinopathy was significantly associated with a self-reported diagnosis of stroke (OR, 2.05; 95% CI, 1.18, 3.57). CONCLUSIONS: The overall prevalence of retinal microvascular abnormalities in this population was relatively higher than that reported in other regions of the world. Retinopathy is associated with the self-reported diagnosis of stroke while AVN was associated with the self-reported diagnosis of CHD, but the remaining retinal lesions were not consistently associated with CCVds. Thus, an examination of retinal microvascular characteristics may offer clues to CCVds and could be a potentially novel biomarkers for CCVds risk.

Selecting the Best Elements from Previous Kidney Tumor Scoring Systems to Restructure Efficient Predictive Models for Surgery Type.

OBJECTIVE: The aim of this work was to select the best elements from previous scoring systems to restructure efficient predictive models for surgery type. METHODS: Sixteen elements were selected from 7 systems (RENAL, PADUA, DAP, ZS, NephRO, ABC, and CI). They were divided into 6 categories (tumor max. size, exophytic/endophytic, correlation with collecting system or sinus, tumor location, contact situation with the parenchyma, invasion depth). Three elements, selected from 3 different categories, were integrated to establish a total of 320 new models. According to AUC rank, optimized models were developed, and these models were divided into 3 sections. An analysis of the distribution of the 6 categories was made to explore the predictive capacities of the models. RESULTS: A total of 166 consecutive patients were included. Seventy-five patients underwent radical nephrectomy operations. The AUC of the 7 systems ranged from 0.81 to 0.844. Three optimized models (AUC 0.88) were developed to predict surgery type. These optimized models were composed of DAP (D), PADUA, (sinus), and ABC; DAP (D), RENAL (N), and ABC; NePhRO (O), PADUA (UCS), and ABC. Two categories ("exophytic/endophytic," p < 0.001; "correlation with collecting system or sinus," p = 0.001) were nonuniformly distributed. CONCLUSIONS: Seven systems held good predictive power for surgery type. Three optimized models were developed. "Correlation with collecting system or sinus" is a critical factor for predicting surgery type.

Hierarchical CNTs@CuMn Layered Double Hydroxide Nanohybrid with Enhanced Electrochemical Performance in H2S Detection from Live Cells.

The precise monitoring of H2S has aroused immense research interest in the biological and biomedical fields since it is exposed as a third endogenous gasotransmitter. Hence, there is an urgent requisite to explore an ultrasensitive and economical H2S detection system. Herein, we report a simple strategy to configure an extremely sensitive electrochemical sensor with a 2D nanosheet-shaped layered double hydroxide (LDH) wrapped carbon nanotubes (CNTs) nanohybrid (CNTs@LDH), where a series of CNTs@CuMn-LDH nanohybrids with varied amounts of LDH nanosheets grafted on a conductive CNTs backbone has been synthesized via a facile coprecipitation approach. Taking advantage of the unique core-shell structure, the integrated electrochemically active CuMn-LDH nanosheets on the conductive CNTs scaffold, the maximum interfacial collaboration, and the superior specific surface area with a plethora of surface active sites and ultrathin LDH layers, the as-prepared CNTs@CuMn-LDH nanoarchitectures have exhibited superb electrocatalytic activity toward H2S oxidation. Under the optimum conditions, the electrochemical sensor based on the CNTs@CuMn-LDH nanohybrid shows remarkable sensing performances for H2S determination in terms of a wide linear range and a low detection limit of 0.3 nM (S/N = 3), high selectivity, reproducibility, and durability. With marvelous efficiency achieved, the proposed sensing platform has been practically used in in situ detection of abiotic H2S efflux produced by sulfate reducing bacteria and real-time in vitro tracking of H2S concentrations from live cells after being excreted by a stimulator which in turn might serve as early diseases diagnosis. Thus, our core-shell hybrid nanoarchitectures fabricated via structural integration strategy will open new horizons in material synthesis, biosensing systems, and clinical chemistry.

A review on electrochemical biosensing platform based on layered double hydroxides for small molecule biomarkers determination.

The development of layered double hydroxides (LDHs), also known as anionic clays with uniform distribution of metal ions and facile exchangeability of intercalated anions, are now appealing an immense deal of attention in synthesis of multifunctional materials. In electrochemical biosensors, LDHs provide stable environment for immobilization of enzymes or other sensing materials and play crucial roles in development of clinical chemistry, point-of-care devices through analysis of various small molecule metabolites excreted by biological processes which in turn serve as molecular biomarkers for medical diagnostics. In this review, we summarize the recent development in fabrication of LDH based nanoarchitectures and their electrocatalytic applications in ultrasensitive in vitro determination of conventional biomarkers, i.e., H2O2, glucose, dopamine and other biomolecules. Moreover, detailed discussion has been compiled to differentiate electrochemical enzymatic and nonenzymatic biosensors, to evaluate useful concentration ranges of H2O2 and glucose for analytical circumstances and to distinguish tumorigenic and normal cells via quantifying the released H2O2 efflux from living cells. Here, we envision that electrochemical sensing platform based on structurally integrated LDH nanohybrids with highly conducting substrates will assist as diseases diagnostic probe further enhancing diagnosis as well as therapeutic window for chronic diseases. Finally, the perspective for fabrication and assembly of LDH electrode is proposed for the future innovation of electrochemical biosensors with high performance making them more reliable for in vitro diagnostics.