Functionalized azirine based scaffolds as endothelin inhibitors for the selective anti-angiogenic activity.

Anti-angiogenic therapy has long been used as an adjunct therapy for the resolution of tumor burden. The current findings describe the synthesis of novel marine-based azirine-containing compounds that exhibit anti-angiogenic mediated anti-tumor activity. Azirine-2-carboxylate inhibited HUVEC-mediated tubulogenesis without causing cell death in a dose-dependent manner. Ex-vivo CAM, in-vivo Matrigel implantation, and ear angiogenesis experiments have all shown that azirine-2-carboxylate effectively inhibits angiogenesis. Furthermore, azirine-2-carboxylate inhibits the migration of ECs without disrupting the preformed tubule network. Azirine-2-carboxylate had adequate intramuscular systemic exposure and inhibited tumor growth in a xenograft mouse model. DARTS analysis, competitive binding assay, and gene expression investigations revealed that azirine-2-carboxylate inhibits endothelin-1-mediated angiogenesis. Overall, the discovery of azirine-2-carboxylate demonstrated a potent inhibition of angiogenesis targeting ET1 and a possible application in anti-angiogenic therapy.

Elevated cardiovascular risk and acute events in hospitalized colon cancer survivors: A decade-apart study of two nationwide cohorts.

BACKGROUND: Over the years, strides in colon cancer detection and treatment have boosted survival rates; yet, post-colon cancer survival entails cardiovascular disease (CVD) risks. Research on CVD risks and acute cardiovascular events in colorectal cancer survivors has been limited. AIM: To compare the CVD risk and adverse cardiovascular outcomes in current colon cancer survivors compared to a decade ago. METHODS: We analyzed 2007 and 2017 hospitalization data from the National Inpatient Sample, studying two colon cancer survivor groups for CVD risk factors, mortality rates, and major adverse events like pulmonary embolism, arrhythmia, cardiac arrest, and stroke, adjusting for confounders via multivariable regression analysis. RESULTS: Of total colon cancer survivors hospitalized in 2007 (n = 177542) and 2017 (n = 178325), the 2017 cohort often consisted of younger (76 vs 77 years), male, African-American, and Hispanic patients admitted non-electively vs the 2007 cohort. Furthermore, the 2017 cohort had higher rates of smoking, alcohol abuse, drug abuse, coagulopathy, liver disease, weight loss, and renal failure. Patients in the 2017 cohort also had higher rates of cardiovascular comorbidities, including hypertension, hyperlipidemia, diabetes, obesity, peripheral vascular disease, congestive heart failure, and at least one traditional CVD (P < 0.001) vs the 2007 cohort. On adjusted multivariable analysis, the 2017 cohort had a significantly higher risk of pulmonary embolism (PE) (OR: 1.47, 95%CI: 1.37-1.48), arrhythmia (OR: 1.41, 95%CI: 1.38-1.43), atrial fibrillation/flutter (OR: 1.61, 95%CI: 1.58-1.64), cardiac arrest including ventricular tachyarrhythmia (OR: 1.63, 95%CI: 1.46-1.82), and stroke (OR: 1.28, 95%CI: 1.22-1.34) with comparable all-cause mortality and fewer routine discharges (48.4% vs 55.0%) (P < 0.001) vs the 2007 cohort. CONCLUSION: Colon cancer survivors hospitalized 10 years apart in the United States showed an increased CVD risk with an increased risk of acute cardiovascular events (stroke 28%, PE 47%, arrhythmia 41%, and cardiac arrest 63%). It is vital to regularly screen colon cancer survivors with concomitant CVD risk factors to curtail long-term cardiovascular complications.

Role of nutraceutical against exposure to pesticide residues: power of bioactive compounds.

Pesticides play a crucial role in modern agriculture, aiding in the protection of crops from pests and diseases. However, their indiscriminate use has raised concerns about their potential adverse effects on human health and the environment. Pesticide residues in food and water supplies are a serious health hazards to the general public since long-term exposure can cause cancer, endocrine disruption, and neurotoxicity, among other health problems. In response to these concerns, researchers and health professionals have been exploring alternative approaches to mitigate the toxic effects of pesticide residues. Bioactive substances called nutraceuticals that come from whole foods including fruits, vegetables, herbs, and spices have drawn interest because of their ability to mitigate the negative effects of pesticide residues. These substances, which include minerals, vitamins, antioxidants, and polyphenols, have a variety of biological actions that may assist in the body's detoxification and healing of harm from pesticide exposure. In this context, this review aims to explore the potential of nutraceutical interventions as a promising strategy to mitigate the toxic effects of pesticide residues.

Imaging Characteristics and Clinical Utility of Half-Dose vs Full-Dose Ultra-Widefield Fluorescein Angiography.

PURPOSE: In early 2022, a fluorescein shortage occurred in the United States. To meet the standard of care for patients who required ultra-wide fundus fluorescein angiography (UWFFA), a regimen of half-dose (250mg) sodium fluorescein (10%) was adopted instead of the full-dose (500mg) at the Cole Eye Institute (CEI). In this paper, we compare the image quality, clinical utility, and the side effect profile of half-dose vs full-dose fluorescein in UWFFA for a cohort of stable patients. DESIGN: Retrospective chart review. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Patients with retinal vascular disease were included if they received half-dose and full-dose UWFFA (Optos California, Dunfermline, UK) within 6 months at the CEI. Eyes were excluded if they received intraocular injections, laser procedures, new immunosuppression, and worsened or improved inflammation on clinical examination. METHODS, INTERVENTION, OR TESTING: Quantitative assessment of vascular leakage was performed using a machine-learning enhanced automated segmentation platform. Leakage from late-phase UWFFA images was compared between half-dose and full-dose images. Qualitative assessment of image quality and relative vascular leakage was performed by 2 masked independent reviewers. Side effects after fluorescein administration were recorded for each patient. MAIN OUTCOME MEASURES: Masked leakage grading and automated leakage scores. RESULTS: There were 52 eyes of 35 patients, 42 (81%) uveitic, 5 (9%) diabetic, and 4 (8%) normal controls. Patients had no change to their visual acuity (LogMAR mean 0.3±0.6), anterior chamber and vitreous cell between UFFWA's. UWFFA images were deemed of equal quality and leakage by both masked reviewers (78-87% agreement, kappa 0.642). Automated leakage analysis showed mildly increased leakage in half-dose images overall (3.8% vs 2.8%, p=0.01), and in the macula (1.5% vs 0.6%, p=0.01). Side effects included nausea (half (n=3, 9%) vs full (n=2, 6%), p=0.69) and urticaria (n=0, 0% vs n=1, 2%, p=0.99) and were not different between doses. CONCLUSIONS: In this cohort, half dose UWFFA produced images that were of similar quality, clinical utility and with a similar side effect profile compared to full dose. Half dose UWFFA can be used to accurately assess the retinal vasculature and could be used primarily as a method to save cost and prevent waste.

RTCpredictor: identification of read-through chimeric RNAs from RNA sequencing data.

Read-through chimeric RNAs are being recognized as a means to expand the functional transcriptome and contribute to cancer tumorigenesis when mis-regulated. However, current software tools often fail to predict them. We have developed RTCpredictor, utilizing a fast ripgrep tool to search for all possible exon-exon combinations of parental gene pairs. We also added exonic variants allowing searches containing common SNPs. To our knowledge, it is the first read-through chimeric RNA specific prediction method that also provides breakpoint coordinates. Compared with 10 other popular tools, RTCpredictor achieved high sensitivity on a simulated and three real datasets. In addition, RTCpredictor has less memory requirements and faster execution time, making it ideal for applying on large datasets.

Investigating the Association between Obstructive Sleep Apnea and Temporomandibular Joint Disorders: A Case-Control Study.

Background: This study aims to explore the connection between obstructive sleep apnea (OSA) and temporomandibular joint disorders (TMD) through a case-control investigation. OSA is a sleep-related breathing disorder that affects breathing during sleep, whereas TMD involves pain and dysfunction in the jaw joint. Understanding any potential association between these two conditions could contribute to improved diagnostic and therapeutic approaches. Materials and Methods: A total of 50 participants were included in both the OSA group and the control group. Participants with diagnosed OSA constituted the OSA group, whereas individuals without OSA formed the control group. TMD symptoms were assessed using standardized diagnostic criteria. Statistical analysis was performed to compare the prevalence of TMD symptoms between the two groups. Results: In the OSA group, 36 out of 50 participants exhibited TMD symptoms, whereas in the control group, 18 out of 50 participants displayed such symptoms. The calculated P value was found to be 0.023, indicating a statistically significant association between OSA and TMD. Conclusion: The findings of this study suggest a notable association between OSA and TMD. Individuals with OSA are more likely to experience TMD symptoms compared to those without OSA. This underscores the importance of considering TMD symptoms in individuals with OSA and vice versa for a comprehensive approach to diagnosis and management.

Culture-Negative Neutrocytic Ascites in a Patient With Cardiac Ascites From End-Stage Heart Failure.

There are two significant groups of infection regarding ascitic fluid: spontaneous bacterial peritonitis (SBP) and culture-negative neutrocytic ascites (CNNA). SBP and CNNA typically occur in patients with cirrhosis. A 46-year-old male with end-stage biventricular heart failure presented with a heart failure exacerbation. He was treated with intravenous diuretics with the improvement of hypervolemia. He remained hospitalized to undergo an evaluation for tricuspid valve repair, but given the severity of his bi-ventricular heart failure, he underwent a heart transplant evaluation. As part of the work-up, he underwent an abdominal ultrasound that was significant for severe ascites but did not note an abnormal hepatic architecture suggestive of cirrhosis. A liver biopsy was then performed, which confirmed no evidence of cirrhosis. His hospitalization was complicated by refractory cardiac ascites, which required a bi-weekly paracentesis. The serum albumin-ascites gradient (SAAG) from his initial paracentesis was 1.4, indicating the etiology was from portal hypertension. The total protein was greater than 2.5 in multiple studies, so the etiology was less concerning for cirrhosis and secondary to his heart failure. About two weeks into his hospital course, he developed a leukocytosis but remained hemodynamically stable and asymptomatic from an infectious standpoint. Analysis of his ascitic fluid initially was negative for infection, but he later developed an elevated total neutrophil count on a subsequent ascitic fluid analysis study. The body fluid culture remained negative for bacterial growth. Hepatology was consulted, and he met the criteria for CNNA, so treatment with ceftriaxone was initiated. After initiating antibiotics, his leukocytosis and elevated ascitic fluid total neutrophil count resolved. Ascitic infections such as CNNA generally occur in patients with liver cirrhosis but may occur in patients without cirrhosis, as observed in our patient. This case highlights that patients with cardiac ascites can develop ascitic fluid infections that may have an impact on their mortality. The precipitating factor that enabled the patient to develop CNNA is unclear but may be related to the translocation of bacteria during his congestive heart failure exacerbation. Although uncommon in a patient with cardiac ascites, an early diagnosis of CNNA and the initiation of antibiotics can be important in preventing patient mortality.

Intranasal Delivery of Carvedilol- and Quercetin-Encapsulated Cationic Nanoliposomes for Cardiovascular Targeting: Formulation and In Vitro and Ex Vivo Studies.

Carvedilol (CVD), an adrenoreceptor blocker, is a hydrophobic Biopharmaceutics Classification System class II drug with poor oral bioavailability due to which frequent dosing is essential to attain pharmacological effects. Quercetin (QC), a polyphenolic compound, is a potent natural antioxidant, but its oral dosing is restricted due to poor aqueous solubility and low oral bioavailability. To overcome the common limitations of both drugs and to attain synergistic cardioprotective effects, we formulated CVD- and QC-encapsulated cationic nanoliposomes (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. We designed CVD- and QC-loaded cationic nanoliposomal (NLPs) in situ gel (CVD/QC-L.O.F.) for intranasal administration. In vitro drug release studies of CVD/QC-L.O.F. (16.25%) exhibited 18.78 ± 0.57% of QC release and 91.38 ± 0.93% of CVD release for 120 h. Ex vivo nasal permeation studies of CVD/QC-L.O.F. demonstrated better permeation of QC (within 96 h), i.e., 75.09% compared to in vitro drug release, whereas CVD permeates within 48 h, indicating the better interaction between cationic NLPs and the negatively charged biological membrane. The developed nasal gel showed a sufficient mucoadhesive property, good spreadability, higher firmness, consistency, and cohesiveness, indicating suitability for membrane application and intranasal administration. CVD-NLPs, QC-NLPs, and CVD/QC-NLPs were evaluated for in vitro cytotoxicity, in vitro ROS-induced cell viability assessment, and a cellular uptake study using H9c2 rat cardiomyocytes. The highest in vitro cellular uptake of CVD/QC-cationic NLPs by H9c2 cells implies the benefit of QC loading within the CVD nanoliposomal carrier system and gives evidence for better interaction of NLPs carrying positive charges with the negatively charged biological cells. The in vitro H2O2-induced oxidative stress cell viability assessment of H9c2 cells established the intracellular antioxidant activity and cardioprotective effect of CVD/QC-cationic NLPs with low cytotoxicity. These findings suggest the potential of cationic NLPs as a suitable drug delivery carrier for CVD and QC combination for the intranasal route in the treatment of various cardiovascular diseases like hypertension, angina pectoris, etc. and for treating neurodegenerative disorders.

Discovery of a polymorphic gene fusion via bottom-up chimeric RNA prediction.

Gene fusions and their chimeric products are commonly linked with cancer. However, recent studies have found chimeric transcripts in non-cancer tissues and cell lines. Large-scale efforts to annotate structural variations have identified gene fusions capable of generating chimeric transcripts even in normal tissues. In this study, we present a bottom-up approach targeting population-specific chimeric RNAs, identifying 58 such instances in the GTEx cohort, including notable cases such as SUZ12P1-CRLF3, TFG-ADGRG7 and TRPM4-PPFIA3, which possess distinct patterns across different ancestry groups. We provide direct evidence for an additional 29 polymorphic chimeric RNAs with associated structural variants, revealing 13 novel rare structural variants. Additionally, we utilize the All of Us dataset and a large cohort of clinical samples to characterize the association of the SUZ12P1-CRLF3-causing variant with patient phenotypes. Our study showcases SUZ12P1-CRLF3 as a representative example, illustrating the identification of elusive structural variants by focusing on those producing population-specific fusion transcripts.

Rehabilitation Using Hybrid Technique for Feeding Plate Fabrication in a 3-Month-Old Infant with Cleft Palate Defect Utilising Digital and Conventional Method: A Case Report.

ABSTRACT: Cleft palate leads to difficulty in suckling, speech abnormalities, dental problems, hearing loss and middle ear infections. Feeding plate acts as a barrier between the oral and nasal cavities allowing the normal development of jaws and enhanced nutritional supply to the patient. Fabrication of the feeding plate using digital means provide better adaptability due to the engagement of all the possible favourable anatomic undercuts, thereby, providing better retention. This case report discusses the hybrid technique including both the digital and conventional means for fabrication of a feeding plate to obturate the defect between the oral and nasal cavity.

Polymer-Based Drug Delivery Systems for Cancer Therapeutics.

Chemotherapy together with surgery and/or radiotherapy are the most common therapeutic methods for treating cancer. However, the off-target effects of chemotherapy are known to produce side effects and dose-limiting toxicities. Novel delivery platforms based on natural and synthetic polymers with enhanced pharmacokinetic and therapeutic potential for the treatment of cancer have grown tremendously over the past 10 years. Polymers can facilitate selective targeting, enhance and prolong circulation, improve delivery, and provide the controlled release of cargos through various mechanisms, including physical adsorption, chemical conjugation, and/or internal loading. Notably, polymers that are biodegradable, biocompatible, and physicochemically stable are considered to be ideal delivery carriers. This biomimetic and bio-inspired system offers a bright future for effective drug delivery with the potential to overcome the obstacles encountered. This review focuses on the barriers that impact the success of chemotherapy drug delivery as well as the recent developments based on natural and synthetic polymers as platforms for improving drug delivery for treating cancer.

Unveiling the Silent Intruder: H. pylori's Hidden Link to Ischemic Heart Disease.

Cardiovascular disease is the leading cause of death. In addition to the well-known risk factors associated with cardiovascular disease, such as age, diabetes mellitus, smoking, hypertension, and obesity, there has been a growing concern regarding cardiac complications stemming from the Gram-negative bacteria Helicobacter pylori. While H. pylori is most commonly associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma, it has also been implicated in extra gastric manifestations, encompassing cardiac, neurologic, ocular, and dermatologic issues. Key virulent factors for coronary artery disease include the vacuolating cytotoxin gene A and the cytotoxin-associated gene A. The most likely pathogenic mechanism of the relationship between H. pylori and coronary artery disease is initiating a chronic inflammatory process associated with infection and the modifications of classic risk factors. These alterations lead to the creation of prothrombotic and procoagulant environments. Here, we review the cardiac manifestations of H. pylori and the underlying pathophysiological mechanisms.

UBA1-CDK16 : A Sex-Specific Chimeric RNA and Its Role in Immune Sexual Dimorphism.

RNA processing mechanisms, such as alternative splicing and RNA editing, have been recognized as critical means to expand the transcriptome. Chimeric RNAs formed by intergenic splicing provide another potential layer of RNA diversification. By analyzing a large set of RNA-Seq data and validating results in over 1,200 blood samples, we identified UBA1-CDK16 , a female-specific chimeric transcript. Intriguingly, both parental genes, are expressed in males and females. Mechanistically, UBA1-CDK16 is produced by cis-splicing between the two adjacent X-linked genes, originating from the inactive X chromosome. A female-specific chromatin loop, formed between the junction sites, facilitates the alternative splicing of its readthrough precursor. This unique chimeric transcript exhibits evolutionary conservation, evolving to be female-specific from non-human primates to humans. Furthermore, our investigation reveals that UBA1-CDK16 is enriched in the myeloid lineage and plays a regulatory role in myeloid differentiation. Notably, female COVID-19 patients who tested negative for this chimeric transcript displayed higher counts of neutrophils, highlighting its potential role in disease pathogenesis. These findings support the notion that chimeric RNAs represent a new repertoire of transcripts that can be regulated independently from the parental genes, and a new class of RNA variance with potential implications in sexual dimorphism and immune responses.

Endothelial Senescence: From Macro- to Micro-Vasculature and Its Implications on Cardiovascular Health.

Endothelial cells line at the most inner layer of blood vessels. They act to control hemostasis, arterial tone/reactivity, wound healing, tissue oxygen, and nutrient supply. With age, endothelial cells become senescent, characterized by reduced regeneration capacity, inflammation, and abnormal secretory profile. Endothelial senescence represents one of the earliest features of arterial ageing and contributes to many age-related diseases. Compared to those in arteries and veins, endothelial cells of the microcirculation exhibit a greater extent of heterogeneity. Microcirculatory endothelial senescence leads to a declined capillary density, reduced angiogenic potentials, decreased blood flow, impaired barrier properties, and hypoperfusion in a tissue or organ-dependent manner. The heterogeneous phenotypes of microvascular endothelial cells in a particular vascular bed and across different tissues remain largely unknown. Accordingly, the mechanisms underlying macro- and micro-vascular endothelial senescence vary in different pathophysiological conditions, thus offering specific target(s) for therapeutic development of senolytic drugs.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Association between lipoprotein (a) and risk of heart failure: A systematic review and meta-analysis of Mendelian randomization studies.

BACKGROUND: Rising incidence of heart failure (HF) in the Western world despite advanced clinical care necessitate exploration of further preventive tools and strategies. Lipoprotein(a) [Lp(a)], recognized as one of the major cardiovascular risk factors has also been implicated as a risk factor for HF. However, existing evidence remains inconclusive and that has led us to perform this meta-analysis. METHODS: PubMed/Medline, EMBASE and Scopus were systematically searched for studies evaluating an association of Lp(a) with occurrence of HF from inception-till November 2023. Random effects models and I2 statistics were used for pooled odds ratio (OR) and heterogeneity assessment. We performed leave one out sensitivity analyses by sequentially removing one study at a time and recalculating the pooled effect size. RESULT: Our search rendered in total 360 studies and after final screening this resulted in 7 Mendelian randomization (MR) design. According to the MR analysis, increasing Lp(a) level were significantly associated with increased risk of HF (OR 1.064, 95 % CI: 1.043-1.086, I2= 97.59 %, P < 0.001). In addition, Leave-one-out sensitivity analysis showed that the effect size did not change substantially by removal of any particular study in MR studies and ORs ranged from 1.051 (when excluding Levin) to a maximum of 1.111 (when excluding Wang or Jiang), hereby confirming the association. CONCLUSION: We were able to show that by meta-analysis of MR data, increasing lipoprotein (a) levels are associated with an increased risk of HF. Whether this is due to a direct effect on heart muscle contraction or whether this is due to an increased risk of ischemic cardiac disease remains to be elucidated.

Genetic variations in tumor-suppressor miRNA-encoding genes and their target genes: focus on breast cancer development and possible therapeutic strategies

MicroRNAs (miRNAs) negatively affect gene expression by binding to their specific mRNAs resulting in either mRNA destruction or translational repression. The aberrant expression of various miRNAs has been associated with a number of human cancer. Oncogenic or tumor-suppressor miRNAs regulate a variety of pathways involved in the development of breast cancer (BC), including cell proliferation, apoptosis, metastasis, cancer recurrence, and chemoresistance. Variations in miRNA-encoding genes and their target genes lead to dysregulated gene expression resulting in the development and progression of BC. The various therapeutic approaches to treat the disease include chemotherapy, radiation therapy, surgical removal, hormone therapy, chemotherapy, and targeted biological therapy. The purpose of the current review is to explore the genetic variations in tumor-suppressor miRNA-encoding genes and their target genes in association with the disease development and prognosis. The therapeutic interventions targeting the variants for better disease outcomes have also been discussed (AU)

A protein-encoding CCDC7 circular RNA inhibits the progression of prostate cancer by up-regulating FLRT3.

Circular RNAs (circRNAs) are a family of endogenous RNAs that have become a focus of biological research in recent years. Emerging evidence has revealed that circRNAs exert biological functions by acting as transcriptional regulators, microRNA sponges, and binding partners with RNA-binding proteins. However, few studies have identified coding circRNAs, which may lead to a hidden repertoire of proteins. In this study, we unexpectedly discovered a protein-encoding circular RNA circCCDC7(15,16,17,18,19) while we were searching for prostate cancer related chimeric RNAs. circCCDC7(15,16,17,18,19) is derived from exon 19 back spliced to exon 15 of the CCDC7 gene. It is significantly downregulated in patients with high Gleason score. Prostate cancer patients with decreased circCCDC7(15,16,17,18,19) expression have a worse prognosis, while linear CCDC7 had no such association. Overexpressed circCCDC7(15,16,17,18,19) inhibited prostate cancer cell migration, invasion, and viability, supporting classification of circCCDC7(15,16,17,18,19) as a bona fide tumor suppressor gene. We provide evidence that its tumor suppressive activity is driven by the protein it encodes, and that circCCDC7(15,16,17,18,19) encodes a secretory protein. Consistently, conditioned media from circCCDC7(15,16,17,18,19) overexpressing cells has the same tumor suppressive activity. We further demonstrate that the tumor suppressive activity of circCCDC7(15,16,17,18,19) is at least partially mediated by FLRT3, whose expression also negatively correlates with Gleason score and clinical prognosis. In conclusion, circCCDC7(15,16,17,18,19) functions as a tumor suppressor in prostate cancer cells through the circCCDC7-180aa secretory protein it encodes, and is a promising therapeutic peptide for prostate cancer.

Microwave-assisted ZnO-decorated carbon urchin resembling 'shish-kebab' morphology with self-healing and enhanced electromagnetic shielding properties.

Herein, inspired by Acacia auriculiformis fruit, the shish-kebab-like growth of ZnO on carbon urchin (ZnO@CU) was designed using microwave radiation, thus leading to a hierarchal 3D structure that can promote multiple internal reflections through polarization centers. This hierarchal structure was then dispersed in a designer polyetherimide (PEI) matrix containing dynamic covalent bonds that can undergo metathesis, triggered by temperature, to harness self-healing properties in the composite. Such key attributes are required for their potential use in EMI shielding applications where frequent repairs are indispensable. Morphological investigation revealed that the ZnO flower was periodically nucleated like 'shish-kebab' structures on CU surfaces. CU was designed from short carbon fibers using a facile modified method. The EMI shielding performance of the resulting composites was investigated in the X-band, illustrating a shielding effectiveness of -40.6 dB for 2 wt% of ZnO@CU loading, and the composite can be preserved after the self-healing procedure. The ZnO 'kebabs' on 'CU shish' facilitated multiple scattering and numerous polarization centers to improve the EMI shielding performances at extremely low filler contents. In addition, the mechanical and thermal properties of the composite showed improved structural integrity and superior resistance to extreme temperatures, respectively. Overall, the proposed ZnO@CU/PEI composite has great potential to fulfill the increasing demands for lightweight EMI shielding materials in many fields.