Role of apoptosis repressor with caspase recruitment domain in human health and chronic diseases.

Apoptosis repressor with caspase recruitment domain (ARC) is a highly potent and multifunctional suppressor of various types of programmed cell death (PCD) (e.g. apoptosis, necroptosis, and pyroptosis) and plays a key role in determining cell fate. Under physiological conditions, ARC is predominantly expressed in terminally differentiated cells, such as cardiomyocytes and skeletal muscle cells. Its expression and activity are tightly controlled by a complicated system consisting of transcription factor (TF), non-coding RNA (ncRNA), and post-translational modification (PTM). ARC dysregulation has been shown to be closely associated with many chronic diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative disease. However, the detailed mechanisms of ARC involved in the progression of these diseases remain unclear to a large extent. In this review, we mainly focus on the regulatory mechanisms of ARC expression and activity and its role in PCD. We also discuss the underlying mechanisms of ARC in health and disease and highlight the potential implications of ARC in the clinical treatment of patients with chronic diseases. This information may assist in developing ARC-based therapeutic strategies for patients with chronic diseases and expand researchers' understanding of ARC.

The first case of multiple myeloma treated with ASCT followed by Anti-BCMA CAR-T cells using retrovirus vector: A case report.

Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.

A Biomimetic Nanocarrier Strategy Targets Ferroptosis and Efferocytosis During Myocardial Infarction.

Background: Myocardial infarction (MI) is characterized by irreversible cardiomyocyte death resulting from an inadequate supply of oxygenated blood to the myocardium. Recent studies have indicated that ferroptosis, a form of regulated cell death, exacerbates myocardial injury during MI. Concurrently, the upregulation of CD47 on the surface of damaged myocardium following MI impairs the clearance of dead cells by macrophages, thereby hindering efferocytosis. In this context, simultaneously inhibiting ferroptosis and enhancing efferocytosis may represent a promising strategy to mitigate myocardial damage post-MI. Methods: In this study, we engineered platelet membrane-coated hollow mesoporous silicon nanoparticles (HMSN) to serve as a drug delivery system, encapsulating ferroptosis inhibitor, Ferrostatin-1, along with an anti-CD47 antibody. We aimed to assess the potential of these nanoparticles (designated as Fer-aCD47@PHMSN) to specifically target the site of MI and evaluate their efficacy in reducing cardiomyocyte death and inflammation. Results: The platelet membrane coating on the nanoparticles significantly enhanced their ability to successfully target the site of myocardial infarction (MI). Our findings demonstrate that treatment with Fer-aCD47@PHMSN resulted in a 38.5% reduction in cardiomyocyte ferroptosis under hypoxia, indicated by decreased lipid peroxidation and increased in vitro. Additionally, Fer-aCD47@PHMSN improved cardiomyocyte efferocytosis by approximately 15% in vitro. In MI mice treated with Fer-aCD47@PHMSN, we observed a substantial reduction in cardiomyocyte death (nearly 30%), decreased inflammation, and significant improvement in cardiac function. Conclusion: Our results demonstrated that the cooperation between the two agents induced anti-ferroptosis effects and enhanced dead cardiomyocyte clearance by macrophage as well as anti-inflammation effects. Thus, our nanoparticle Fer-aCD47@PHMSN provides a new therapeutic strategy for targeted therapy of MI.

Design of 1.1T/300 mm Bitter-type magnet for gyro-traveling-wave tube with power consumption optimization theory.

To improve the portability of magnets in gyrotron devices, we designed a compact Bitter-type magnet with power consumption optimization theory. This magnet operates at room temperature in a small volume. The theory revises existing electromagnetic theory for non-uniform structural Bitter-type magnets and achieves the lowest energy consumption through iterative optimization. To extend the magnetic field homogeneity region, the ferromagnetic material armature is applied to the Bitter-type system without additional power consumption. Unlike previous manual designs, the proposed Bitter-type magnets can obtain optimal parameters with a significant reduction in computing time. Through the introduction of correction factors, we improve accuracy through multiple verifications of simulations and experiments. On this basis, a room-temperature Bitter-type magnet system for Ka-band fundamental mode gyrotron amplifiers is designed. Its maximum magnetic field strength is 1.1 T, and the length of the homogeneity region is 300 mm. Through optimization, its energy consumption is only 27.5 kW.

Advanced Nanomedicine Approaches for Myocardial Infarction Treatment.

Myocardial infarction, usually caused by the rupture of atherosclerotic plaque, leads to irreversible ischemic cardiomyocyte death within hours followed by impaired cardiac performance or even heart failure. Current interventional reperfusion strategies for myocardial infarction still face high mortality with the development of heart failure. Nanomaterial-based therapy has made great progress in reducing infarct size and promoting cardiac repair after MI, although most studies are preclinical trials. This review focuses primarily on recent progress (2016-now) in the development of various nanomedicines in the treatment of myocardial infarction. We summarize these applications with the strategy of mechanism including anti-cardiomyocyte death strategy, activation of neovascularization, antioxidants strategy, immunomodulation, anti-cardiac remodeling, and cardiac repair.

A novel circPIK3C2A/miR­31­5p/TFRC axis drives ferroptosis and accelerates myocardial injury.

Iron overload is common in cardiovascular disease, it is also the factor that drives ferroptosis. Noncoding RNAs play an important role in heart disease; however, their regulatory role in iron overload-mediated ferroptosis remains much unknown. In our study, the iron overload model in mice was constructed through a high-iron diet, and ammonium iron citrate  treatment was used to mimic iron overload in vitro. We found iron overload induced ferroptosis in cardiomyocytes, which was dependent on the high expression of transferrin receptor (TFRC). MiR-31-5p was downregulated during iron overload; it inhibited cardiomyocyte ferroptosis by targeting TFRC. CircPIK3C2A, a highly expressed circRNA in the heart, was upregulated when iron was overloaded. CircPIK3C2A enhanced the expression of TFRC by sponging miR-31-5p and promoted ferroptosis during iron overload. Our results reveal a novel mechanistic insight into noncoding RNA-based ferroptosis and identify the circPIK3C2A/miR-31-5p/TFRC axis as a promising therapeutic target for myocardial damage.

Oxidative modification of miR-30c promotes cardiac fibroblast proliferation via CDKN2C mismatch.

The response of cardiac fibroblast proliferation to detrimental stimuli is one of the main pathological factors causing heart remodeling. Reactive oxygen species (ROS) mediate the proliferation of cardiac fibroblasts. However, the exact molecular mechanism remains unclear. In vivo, we examined the oxidative modification of miRNAs with miRNA immunoprecipitation with O8G in animal models of cardiac fibrosis induced by Ang II injection or ischemia‒reperfusion injury. Furthermore, in vitro, we constructed oxidation-modified miR-30c and investigated its effects on the proliferation of cardiac fibroblasts. Additionally, luciferase reporter assays were used to identify the target of oxidized miR-30c. We found that miR-30c oxidation was modified by Ang II and PDGF treatment and mediated by excess ROS. We demonstrated that oxidative modification of G to O8G occurred at positions 4 and 5 of the 5' end of miR-30c (4,5-oxo-miR-30c), and this modification promoted cardiac fibroblast proliferation. Furthermore, CDKN2C is a negative regulator of cardiac fibroblast proliferation. 4,5-oxo-miR-30c misrecognizes CDKN2C mRNA, resulting in a reduction in protein expression. Oxidized miR-30c promotes cardiac fibroblast proliferation by mismatch mRNA of CDKN2C.

A neural network-based algorithm for the reconstruction and filtering of single particle trajectory in magnetic particle tracking.

Magnetic particle tracking (MPT) is a recently developed non-invasive measurement technique that has gained popularity for studying dense particulate or granular flows. This method involves tracking the trajectory of a magnetically labeled particle, the field of which is modeled as a dipole. The nature of this method allows it to be used in opaque environments, which can be highly beneficial for the measurement of dense particle dynamics. However, since the magnetic field of the particle used is weak, the signal-to-noise ratio is usually low. The noise from the measuring devices contaminates the reconstruction of the magnetic tracer's trajectory. A filter is then needed to reduce the noise in the final trajectory results. In this work, we present a neural network-based framework for MPT trajectory reconstruction and filtering, which yields accurate results and operates at very high speed. The reconstruction derived from this framework is compared to the state-of-the-art extended Kalman filter-based reconstruction.

Rapid response in relapsed follicular lymphoma to novel anti-CD19 CAR-T therapy with pseudo-progression and cytomegalovirus infection: A case report.

CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas. Most of these CARs were generated by lentivirus. With the exception of Yescarta and Tecartus, few patients with relapsed-/refractory- lymphoma have been treated clinically with a CARs using retroviral vector (RV). Here, we reported a relapsed/refractory grade 2 follicular lymphoma patient with multiple chemotherapy failures, and was treated with a novel CD19 CAR-T cell manufactured from a RV. After tumor burden was reduced with Obinutuzumab and Duvelisib, the patient was infused novel CD19 CAR-T cells at a dose of 3 × 106 cells/ kg. Then he experienced a rapid response and achieved almost complete remission by day 26. Only grade 2 CRS, bilateral submaxillary lymph node enlargement and cytomegalovirus (CMV) infection occurred without neurotoxicity, and the patient's condition improved after a series of symptomatic treatments. In addition, CAR copy number peaked at 532,350 copies/µg on day 15 and continued to expand for 5 months. This may be the first case report of RV preparation of novel CD19 CAR-T cells for direct treatment of recurrent follicular lymphoma. We will observe its long-term efficacy and conduct trials in more patients in the future.

Engineered Multivalent Nanobodies Efficiently Neutralize SARS-CoV-2 Omicron Subvariants BA.1, BA.4/5, XBB.1 and BQ.1.1.

Most available neutralizing antibodies are ineffective against highly mutated SARS-CoV-2 Omicron subvariants. Therefore, it is crucial to develop potent and broad-spectrum alternatives to effectively manage Omicron subvariants. Here, we constructed a high-diversity nanobody phage display library and identified nine nanobodies specific to the SARS-CoV-2 receptor-binding domain (RBD). Five of them exhibited cross-neutralization activity against the SARS-CoV-2 wild-type (WT) strain and the Omicron subvariants BA.1 and BA.4/5, and one nanobody demonstrated marked efficacy even against the Omicron subvariants BQ.1.1 and XBB.1. To enhance the therapeutic potential, we engineered a panel of multivalent nanobodies with increased neutralizing potency and breadth. The most potent multivalent nanobody, B13-B13-B13, cross-neutralized all tested pseudoviruses, with a geometric mean of the 50% inhibitory concentration (GM IC50) value of 20.83 ng/mL. An analysis of the mechanism underlying the enhancement of neutralization breadth by representative multivalent nanobodies demonstrated that the strategic engineering approach of combining two or three nanobodies into a multivalent molecule could improve the affinity between a single nanobody and spike, and could enhance tolerance toward escape mutations such as R346T and N460K. Our engineered multivalent nanobodies may be promising drug candidates for treating and preventing infection with Omicron subvariants and even future variants.

CircHIPK3 targets DRP1 to mediate hydrogen peroxide-induced necroptosis of vascular smooth muscle cells and atherosclerotic vulnerable plaque formation.

INTRODUCTION: Necroptosis triggered by H2O2 is hypothesized to be a critical factor in the rupture of atherosclerotic plaques, which may precipitate acute cardiovascular events. Nevertheless, the specific regulatory molecules of this development remain unclear. We aims to elucidate a mechanism from the perspective of circular RNA. OBJECTIVES: There are few studies on circRNA in VSMCs necroptosis. The objective of our research is to shed light on the intricate roles that circHIPK3 plays in the process of necroptosis in VSMCs and the development of atherosclerotic plaques that are prone to rupture. Our study elucidates the specific molecular mechanisms by which circHIPK3 regulates necroptosis and atherosclerotic vulnerable plaque formation through targeted proteins. Identifying this mechanism at the cellular level offers a molecular framework for understanding plaque progression and stability regulation, as well as a potential biomarker for the prognosis of susceptible atherosclerotic plaques. METHODS: We collected clinical vascular tissue for HE staining and Masson staining to determine the presence and stability of plaques. Then, NCBI database was used to screen out circRNA with elevated expression level in plaque tissue, and the up-regulated circRNA, circHIPK3, was verified by qRT-PCR and FISH. Further, we synthesized circHIPK3's small interference sequence and overexpressed plasmid in vitro, and verified its regulation effect on necroptosis of VSMCs under physiological and pathological conditions by WB, qRT-PCR and PI staining. Through RNA pull down, mass spectrometry and RNA immunoprecipitation, DRP1 was identified as circHIPK3 binding protein and was positively regulated by circHIPK3. Meanwhile, on the basis of silencing of DRP1, the regulation of circHIPK3 on necroptosis is verified to be mediated by DRP1. Finally, we validated the regulation of circHIPK3 on vulnerable plaque formation in ApoE-/- mice. RESULTS: We investigated that circHIPK3 was highly expressed in vulnerable plaques, and the increase in expression level promoted H2O2 induced necroptosis of VSMCs. CircHIPK3 targeted the protein DRP1, leading to an elevation in mitochondrial division rate, resulting in increased reactive oxygen species and impaired mitochondrial function, ultimately leading to necroptosis of VSMCs and vulnerable plaque formation. CONCLUSION: CircHIPK3 interact with DRP1 involve in H2O2 induced Mitochondrial damage and necroptosis of VSMCs, and Silencing circHIPK3 in vivo can reduce atherosclerotic vulnerable plaque formation. Our research findings may have applications in providing diagnostic biomarkers for vulnerable plaques.

PLD2 deletion ameliorates sepsis-induced cardiomyopathy by suppressing cardiomyocyte pyroptosis via the NLRP3/caspase 1/GSDMD pathway.

OBJECTIVE: Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication. Phospholipase D2 (PLD2) is crucial in mediating inflammatory reactions and is associated with the prognosis of patients with sepsis. Whether PLD2 is involved in the pathophysiology of SICM remains unknown. This study aimed to investigate the effect of PLD2 knockout on SICM and to explore potential mechanisms. METHODS: The SICM model was established using cecal ligation and puncture in wild-type and PLD2-knockout mice and lipopolysaccharide (LPS)-induced H9C2 cardiomyocytes. Transfection with PLD2-shRNA lentivirus and a PLD2 overexpression plasmid were used to interfere with PLD2 expression in H9C2 cells. Cardiac pathological alterations, cardiac function, markers of myocardial injury, and inflammatory factors were used to evaluate the SICM model. The expression of pyroptosis-related proteins (NLRP3, cleaved caspase 1, and GSDMD-N) was assessed using western blotting, immunofluorescence, and immunohistochemistry. RESULTS: SICM mice had myocardial tissue damage, increased inflammatory response, and impaired heart function, accompanied by elevated PLD2 expression. PLD2 deletion improved cardiac histological changes, mitigated cTNI production, and enhanced the survival of the SICM mice. Compared with controls, PLD2-knockdown H9C2 exhibits a decrease in inflammatory markers and lactate dehydrogenase production, and scanning electron microscopy results suggest that pyroptosis may be involved. The overexpression of PLD2 increased the expression of NLRP3 in cardiomyocytes. In addition, PLD2 deletion decreased the expression of pyroptosis-related proteins in SICM mice and LPS-induced H9C2 cells. CONCLUSION: PLD2 deletion is involved in SICM pathogenesis and is associated with the inhibition of the myocardial inflammatory response and pyroptosis through the NLRP3/caspase 1/GSDMD pathway.

Optimizing Energy Levels and Improving Film Compactness in PbS Quantum Dot Solar Cells by Silver Doping.

PbS quantum dot (QD) solar cells harvest near-infrared solar radiation. Their conventional hole transport layer has limited hole collection efficiency due to energy level mismatch and poor film quality. Here, how to resolve these two issues by using Ag-doped PbS QDs are demonstrated. On the one hand, Ag doping relieves the compressive stress during layer deposition and thus improves film compactness and homogeneity to suppress leakage currents. On the other hand, Ag doping increases hole concentration, which aligns energy levels and increases hole mobility to boost hole collection. Increased hole concentration also broadens the depletion region of the active layer, decreasing interface charge accumulation and promoting carrier extraction efficiency. A champion power conversion efficiency of 12.42% is achieved by optimizing the hole transport layer in PbS QD solar cells, compared to 9.38% for control devices. Doping can be combined with compressive strain relief to optimize carrier concentration and energy levels in QDs, and even introduce other novel phenomena such as improved film quality.

Circular RNA-circPan3 attenuates cardiac hypertrophy via miR-320-3p/HSP20 axis.

BACKGROUND: Circular RNAs are enriched in cardiac tissue and play important roles in the pathogenesis of heart diseases. In this study, we aimed to investigate the regulatory mechanism of a conserved heart-enriched circRNA, circPan3, in cardiac hypertrophy. METHODS: Cardiac hypertrophy was induced by isoproterenol. The progression of cardiomyocyte hypertrophy was assessed by sarcomere organization staining, cell surface area measurement, and expression levels of cardiac hypertrophy markers. RNA interactions were detected by RNA pull-down assays, and methylated RNA immunoprecipitation was used to detect m6A level. RESULTS: The expression of circPan3 was downregulated in an isoproterenol-induced cardiac hypertrophy model. Forced expression of circPan3 attenuated cardiomyocyte hypertrophy, while inhibition of circPan3 aggravated cardiomyocyte hypertrophy. Mechanistically, circPan3 was an endogenous sponge of miR-320-3p without affecting miR-320-3p levels. It elevated the expression of HSP20 by endogenously interacting with miR-320-3p. In addition, circPan3 was N6-methylated. Stimulation by isoproterenol downregulated the m6A eraser ALKBH5, resulting in N6-methylation and destabilization of circPan3. CONCLUSIONS: Our research is the first to report that circPan3 has an antihypertrophic effect in cardiomyocytes and revealed a novel circPan3-modulated signalling pathway involved in cardiac hypertrophy. CircPan3 inhibits cardiac hypertrophy by targeting the miR-320-3p/HSP20 axis and is regulated by ALKBH5-mediated N6-methylation. This pathway could provide potential therapeutic targets for cardiac hypertrophy.

Morphological risk of acute type A aortic dissection in the mildly to moderately dilated aorta.

OBJECTIVES: This study aimed to analyse and determine the role of aortic length and curvature in the pathogenesis of acute type A aortic dissection (ATAAD) with ascending aortic diameters (AADs) <5 cm. METHODS: We reviewed the clinical and imaging data of patients with ATAAD (n = 201) and ascending aortic dilation (n = 83). Thoracic aortic bending index (TABI) was used to quantify aortic curvature and analyse its role in ATAAD below the diameter risk threshold. RESULTS: The AAD was <5.0 and <4.0 cm in 78% and 37% of patients with ATAAD, respectively. The median ascending aortic length (AAL) was 104.6 mm (Q1-Q3, 96.5-113.6 mm), and in 62.7% of patients, it was <11 cm. The median TABI was 14.99 mm/cm (Q1-Q3, 14.18-15.86 mm/cm). Patients with ATAAD and those with aortic dilation were matched for AAD, age, sex, height and other clinical factors. After matched, the dissection group had higher AALs (median, 102.9 mm; Q1-Q3, 96.0-112.5 mm vs median, 88.2 mm; Q1-Q3, 83.7-95.9 mm; P < 0.001) and TABI (median, 14.84 mm/cm; Q1-Q3, 14.06-15.83 mm/cm vs median, 13.55 mm/cm; Q1-Q3, 13.03-14.28 mm/cm; P < 0.001). According to the regression analysis, the area under the curve required to distinguish patients with ATAAD from those with aortic dilation was 0.831 in AAL, 0.837 in TABI and 0.907 when AAL was combined with TABI. CONCLUSIONS: The patients with ATAAD had higher AAL and TABI than those with aortic dilation. The combination of TABI and AAL might be a potential morphological marker for determining ATAAD risk below the current aortic diameter risk threshold.

Circular RNA-circLRP6 protects cardiomyocyte from hypoxia-induced apoptosis by facilitating hnRNPM-mediated expression of FGF-9.

Coronary atherosclerosis-induced myocardial ischemia leads to cardiomyocyte apoptosis. The regulatory mechanisms for cardiomyocyte apoptosis have not been fully understood. Circular RNAs are non-coding RNAs which play important roles in heart function maintenance and progression of heart diseases by regulating gene transcription and protein translation. Here, we reported a conserved cardiac circular RNA, which is generated from the second exon of LRP6 and named circLRP62-2 . CircLRP62-2 can protect cardiomyocyte from hypoxia-induced apoptosis. The expression of circLRP62-2 in cardiomyocytes was down-regulated under hypoxia, while forced expression of circLRP62-2 inhibited cell apoptosis. Normally, circLRP62-2 was mainly localized in the nucleus. Under hypoxia, circLRP62-2 is associated with heterogeneous nuclear ribonucleoprotein M (hnRNPM) to be translocated into the cytoplasm. It recruited hnRNPM to fibroblast growth factor 9 (FGF9) mRNA to enhance the expression of FGF9 protein, promoting hypoxia-adaption and viability of cardiomyocytes. In summary, this study uncovers a new inhibitor of apoptosis and reveals a novel anti-apoptotic pathway composed of circLRP62-2 , hnRNPM, and FGF9, which may provide therapeutic targets for coronary heart disease and ischemic myocardial injury.

O-GlcNAcylation: cellular physiology and therapeutic target for human diseases.

O-linked-ß-N-acetylglucosamine (O-GlcNAcylation) is a distinctive posttranslational protein modification involving the coordinated action of O-GlcNAc transferase and O-GlcNAcase, primarily targeting serine or threonine residues in various proteins. This modification impacts protein functionality, influencing stability, protein-protein interactions, and localization. Its interaction with other modifications such as phosphorylation and ubiquitination is becoming increasingly evident. Dysregulation of O-GlcNAcylation is associated with numerous human diseases, including diabetes, nervous system degeneration, and cancers. This review extensively explores the regulatory mechanisms of O-GlcNAcylation, its effects on cellular physiology, and its role in the pathogenesis of diseases. It examines the implications of aberrant O-GlcNAcylation in diabetes and tumorigenesis, highlighting novel insights into its potential role in cardiovascular diseases. The review also discusses the interplay of O-GlcNAcylation with other protein modifications and its impact on cell growth and metabolism. By synthesizing current research, this review elucidates the multifaceted roles of O-GlcNAcylation, providing a comprehensive reference for future studies. It underscores the potential of targeting the O-GlcNAcylation cycle in developing novel therapeutic strategies for various pathologies.

Design and verification of a backward wave oscillation suppression circuit for the Ka-band gyrotron travelling-wave tube.

Backward wave oscillation seriously degrades the stability of gyrotron travelling-wave tubes (gyro-TWTs), especially during high average/continuous wave operation. To solve this problem, a selective mode suppression structure (SMSS) based on the mode coupling principle is proposed and applied in the nonlinear beam-wave interaction region to suppress the parasitic TE11 mode. It is capable of obtaining a high power and improving the tube stability. Simulation results demonstrate that the SMSS can raise the starting current from 10 to 18 A and the starting pitch factor from 1.2 to 1.6. Based on this proposed circuit, a Ka-band TE01 mode gyro-TWT was designed, and the particle-in-cell simulation shows that it can achieve a saturated output power of over 150 kW from 29.7 to 31.7 GHz with a velocity spread of 2.2%. For verification, a SMSS is manufactured and cold tested. The measurement of S-parameters reveals that it can effectively suppress the parasitic TE11 mode.

piRNA-823 is a novel potential therapeutic target in aortic dissection.

Aortic dissection (AD) presents a medical challenge for clinicians. Here, to determine the role of a novel small non-coding piRNA-823 (piR-823) in AD, murine and human aorta from patients with AD were used. A high expression levels of piR-823 were found in patients with AD. Using performed loss- and gain-of-function assays in vitro and in vivo, we explore the regulatory effect of piR-823 on vascular smooth muscle cells (VSMCs) and AD. piR-823 obviously facilitates the proliferation, migration, and phenotypic transformation of VSMCs with or without nicotine treatment. piR-823 directly binds and suppresses histone deacetylase 1 (HDAC1) expression, and regulates the acetylation of histone 3 (H3) via H3K9ac and H3K27ac, eventually, VSMC functions and AD. To consolidate our findings, AD murine model was performed, and we observed that piR-823 antagomir strongly inhibited the pathogenesis of AD through regulating vascular remodeling. Thus, our study finds a potential target for the prevention and treatment strategy for nicotine-induced AD.

Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications.

Lung cancer (LC) is a heterogeneous disease with high malignant degree, rapid growth, and early metastasis. The clinical outcomes of LC patients are generally poor due to the insufficient elucidation of pathological mechanisms, low efficiency of detection and assessment methods, and lack of individualized therapeutic strategies. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA), are endogenous regulators that are widely involved in the modulation of almost all aspects of life activities, from organogenesis and aging to immunity and cancer. They commonly play vital roles in various biological processes by regulating gene expression via their interactions with DNA, RNA, or protein. An increasing amount of studies have demonstrated that ncRNAs are closely correlated with the initiation and development of LC. Their dysregulation promotes the progression of LC via distinct mechanisms, such as influencing protein activity, activating oncogenic signaling pathways, or altering specific gene expression. Furthermore, some ncRNAs present certain clinical values as biomarker candidates and therapeutic targets for LC patients. A complete understanding of their mechanisms in LC progression may be highly beneficial to developing ncRNA-based therapeutics for LC patients. This review mainly focuses on the intricate mechanisms of miRNA, lncRNA, and circRNA involved in LC progression and discuss their underlying applications in LC treatment.