Gut microbiota-lncRNA/circRNA crosstalk: implications for different diseases.

The gut microbiota features an abundance of diverse microorganisms and represents an important component of human physiology and metabolic homeostasis, indicating their roles in a wide array of physiological and pathological processes in the host. Maintaining balance in the gut microbiota is critical for normal functionality as microbial dysbiosis can lead to the occurrence and development of diseases through various mechanisms. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are non-coding RNAs that perform important regulatory functions for many processes. Furthermore, the gut microbiota and lncRNAs/circRNAs are known to interact in a range of both physiological and pathological activities. In this article, we review existing research relevant to the interaction between the gut microbiota and lncRNAs/circRNAs and investigate the role of their crosstalk in the pathogenesis of different diseases. Studies have shown that, the gut microbiota can target lncRNAs ENO1-IT1, BFAL1, and LINC00152 to regulate colorectal cancer development via various signaling pathways. In addition, the gut microbiota can influence mental diseases and lung tumor metastasis by modulating circRNAs such as circNF1-419, circ_0001239, circHIPK2 and mmu_circ_0000730. These findings provide a theoretical basis for disease prevention and treatment and suggest that gut microbiota-lncRNA/circRNA crosstalk has high clinical value.

Functionalized Blood Small Extracellular Vesicles with Polydopamine Nanoparticles for Chemo-Thermal Therapy.

Small extracellular vesicles (sEVs) hold considerable promise for drug delivery due to their natural origin and inherent qualities. However, their clinical application is impeded by two main challenges: low yield and potential side effects. Therefore, it is crucial to obtain substantial quantities of sEVs that adhere to rigorous biosafety standards to ensure successful translation into clinical practice. To address this need, we propose exploring optimized methods for sourcing and separating sEVs, taking inspiration from clinical blood transfusion. In particular, we have identified blood sEVs as a viable alternative and developed a novel separation technique for their isolation. Our approach involves incubating dopamine solution with serum, resulting in the formation of polydopamine (PDA) nanoparticles on the surface of blood sEVs. These nanoparticles have minimal impact on blood sEVs, facilitating their easy separation under standard centrifugal conditions with high purity. This innovative technique enables the development of nanocarriers using blood sEVs with efficient drug-loading capabilities and enhanced pharmacokinetics. Additionally, the incorporation of PDA nanoparticles imparts a photothermal effect to the nanomedicines, enabling the integration of chemotherapy and photothermal therapy. Moreover, the photothermal effect holds the potential to facilitate the membrane fusion of sEVs and cells. In summary, our straightforward surface functionalization technique utilizing PDA effectively isolates blood sEVs and enables chemo-thermal tumor therapy. This approach significantly enhances the feasibility of translating sEV-based nanomedicines into clinical applications.

Structure-guided conversion from an anaplastic lymphoma kinase inhibitor into Plasmodium lysyl-tRNA synthetase selective inhibitors.

Aminoacyl-tRNA synthetases (aaRSs) play a central role in the translation of genetic code, serving as attractive drug targets. Within this family, the lysyl-tRNA synthetase (LysRS) constitutes a promising antimalarial target. ASP3026, an anaplastic lymphoma kinase (ALK) inhibitor was recently identified as a novel Plasmodium falciparum LysRS (PfLysRS) inhibitor. Here, based on cocrystal structures and biochemical experiments, we developed a series of ASP3026 analogues to improve the selectivity and potency of LysRS inhibition. The leading compound 36 showed a dissociation constant of 15.9 nM with PfLysRS. The inhibitory efficacy on PfLysRS and parasites has been enhanced. Covalent attachment of L-lysine to compound 36 resulted in compound 36K3, which exhibited further increased inhibitory activity against PfLysRS but significantly decreased activity against ALK. However, its inhibitory activity against parasites did not improve, suggesting potential future optimization directions. This study presents a new example of derivatization of kinase inhibitors repurposed to inhibit aaRS.

THOC6 is a novel biomarker of glioma and a target of anti-glioma drugs: An analysis based on bioinformatics and molecular docking.

Glioma is a typical malignant tumor of the nervous system. It is of great significance to identify new biomarkers for accurate diagnosis of glioma. In this context, THOC6 has been studied as a highly diagnostic prognostic biomarker, which contributes to improve the dilemma in diagnosing gliomas. We used online databases and a variety of statistical methods, such as Wilcoxon rank sum test, Dunn test and t test. We analyzed the mutation, location and expression profile of THOC6, revealing the network of THOC6 interaction with disease. Wilcoxon rank sum test showed that THOC6 is highly expressed in gliomas (P < 0.001). Dunn test, Wilcoxon rank sum test and t test showed that THOC6 expression was correlated with multiple clinical features. Logistic regression analysis further confirmed that THOC6 gene expression was a categorical dependent variable related to clinical features of poor prognosis. Kaplan-Meier survival analysis showed that the overall survival (OS) of glioma patients with high expression of THOC6 was poor (P < 0.001). Both univariate (P < 0.001) and multivariate (P = 0.04) Cox analysis confirmed that THOC6 gene expression was an independent risk factor for OS in patients with glioma. ROC curve analysis showed that THOC6 had a high diagnostic value in glioma (AUC = 0.915). Based on this, we constructed a nomogram to predict patient survival. Enrichment analysis showed that THOC6 expression was associated with multiple signal pathways. Immuno-infiltration analysis showed that the expression of THOC6 in glioma was closely related to the infiltration level of multiple immune cells. Molecular docking results showed that THOC6 might be the target of anti-glioma drugs. THOC6 is a novel diagnostic factor and prognostic biomarker of glioma.

Pt-Ru bimetallic nanoclusters with peroxidase-like activity for antibacterial therapy.

Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 µg/mL and 16 µg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.

Nanozyme-based visual diagnosis and therapeutics for myocardial infarction: The application and strategy.

BACKGROUND: Myocardial infarction (MI) is a heart injury caused by ischemia and low oxygen conditions. The occurrence of MI lead to the activation of a large number of neutrophils and macrophages, inducing severe inflammatory injury. Meanwhile, the inflammatory response produces much more free radicals, further exacerbating the inflammatory response and tissue damage. Efforts are being dedicated to developing antioxidants and enzymes, as well as small molecule drugs, for treating myocardial ischemia. However, poor pharmacokinetics and potential side effects limit the clinical application of these drugs. Recent advances in nanotechnology have paved new pathways in biomedical and healthcare environments. Nanozymes exhibit the advantages of biological enzymes and nanomaterials, including with higher catalytic activity and stability than natural enzymes. Thus, nanozymes provide new possibilities for the diagnosis and treatment of oxidative stress and inflammation-related diseases. AIM OF REVIEW: We describe the application of nanozymes in the diagnosis and therapy of MI, aiming to bridge the gap between the diagnostic and therapeutic needs of MI. KEY SCIENTIFIC CONCEPTS OF REVIEW: We describe the application of nanozymes in the diagnosis and therapy of MI, and discuss the new strategies for improving the diagnosis and treatment of MI. We review in detail the applications of nanozymes to achieve highly sensitive detection of biomarkers of MI. Due to their unique enzyme catalytic capabilities, nanozymes have the ability to sensitively detect biomolecules through colorimetric, fluorescent, and electrochemical assays. In addition, nanozymes exhibit excellent antioxidase-mimicking activity to treat MI by modulating reduction/oxidation (REDOX) homeostasis. Nanozymes can also passively or actively target MI tissue sites, thereby protecting ischemic myocardial tissue and reducing the infarct area. These innovative applications of nanozymes in the field of biomedicine have shown promising results in the diagnosis and treatment of MI, offering a novel therapeutic strategy.

CircTMEM165 facilitates endothelial repair by modulating mitochondrial fission via miR-192/SCP2 in vitro and in vivo.

Constitutive explorations indicate a correlation between circular RNAs (circRNAs) and cardiovascular diseases. However, the involvement of circRNAs in endothelial recuperation and in-stent restenosis (ISR) remains underexplored. CircTMEM165 has first been reported to be highly expressed in hypoxic human umbilical vein endothelial cells (HUVECs). Here, we identified that circTMEM165 was downregulated in ISR patients, inversely correlating with ISR severity. Functionally, circTMEM165 was found to be abundant in endothelial cells, inhibiting inflammation, and adhesion. Particularly, we first observed that circTMEM165 could alleviate HUVECs apoptosis and mitochondrial fission induced by lipopolysaccharide (LPS). Mechanistically, circTMEM165, as a miR-192-3p sponge, enhancing SCP2 expression, which serves as a critical regulator of HUVECs biological functions. Moreover, in vivo, circTMEM165 attenuated intimal hyperplasia and facilitated repair following classic rat carotid artery balloon injury model. These findings investigated the circTMEM165-miR-192-3p-SCP2 axis as a critical determinant of endothelial health and a potential biomarker and therapeutic target for vascular disorders.

Sialylated glycoproteins and sialyltransferases in digestive cancers: Mechanisms, diagnostic biomarkers, and therapeutic targets.

Sialic acid (SA), as the ultimate epitope of polysaccharides, can act as a cap at the end of polysaccharide chains to prevent their overextension. Sialylation is the enzymatic process of transferring SA residues onto polysaccharides and is catalyzed by a group of enzymes known as sialyltransferases (SiaTs). It is noteworthy that the sialylation level of glycoproteins is significantly altered when digestive cancer occurs. And this alteration exhibits a close correlation with the progression of these cancers. In this review, from the perspective of altered SiaTs expression levels and changed glycoprotein sialylation patterns, we summarize the pathogenesis of gastric cancer (GC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC). Furthermore, we propose potential early diagnostic biomarkers and prognostic indicators for different digestive cancers. Finally, we summarize the therapeutic value of sialylation in digestive system cancers.

LncRNAs associated with lymph node metastasis in thyroid cancer based on TCGA database.

OBJECTIVE: Long non-coding RNA (lncRNA), especially RNA associated with lymph node metastasis, plays an important role in the development of cancer. Identifying metastasis related lncRNAs and exploring their clinical significance can guide the treatment and prognosis of thyroid cancer patients. METHODS: RNA expression and clinical data of thyroid cancer was derived from The Cancer Genome Atlas (TCGA) database, while the survival data was obtained from the ULCAN database. R language and SPSS software were used to analyze the correlation between lncRNA and lymph node metastasis of thyroid cancer and the lncRNAs associated with lymph node metastasis were screened. RESULT: 10 lncRNAs showed significant differential expression in thyroid cancer with and without lymph node metastasis. Four lncRNAs (LRRC52-AS1, AP002358.1, AC004847.1, and AC254633.1) were overexpressed in metastatic thyroid cancer, while six lncRNAs (SLC26A4-AS1, LINC01886, LINC01789, AF131216.3, AC062015.1, and AL031710.1) were underexpressed. The expression levels of these lncRNAs were associated with the clinical staging of tumors. Cox regression analysis further showed that elevated expression levels of AP002358.1 and LRRC52-AS1 were associated with poor prognosis in patients with thyroid cancer. In addition, analysis of the UALCAN database indicated that these two lncRNAs were significantly overexpressed in thyroid cancer compared to other cancers, and the expression levels of AF131216.3 and AL031710.1 were associated with progression-free survival in thyroid cancer patients. CONCLUSION: These lncRNAs may play crucial roles in the development and progression of thyroid cancer and could serve as potential markers for predicting tumor metastasis, clinical stage, and patient prognosis.

Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.

Notch signaling pathway is a highly conserved system of cell-to-cell communication that participates in various biological processes, such as stem cell maintenance, cell fate decision, cell proliferation and death during homeostasis and development. Dysregulation of Notch signaling has been associated with many aspects of cancer biology, such as maintenance of cancer stem-like cells (CSCs), cancer cell metabolism, angiogenesis and tumor immunity. Particularly, Notch signaling can regulate antitumor or pro-tumor immune cells within the tumor microenvironment (TME). Currently, Notch signaling has drawn significant attention in the therapeutic development of cancer treatment. In this review, we focus on the role of Notch signaling pathway in remodeling tumor immune microenvironment. We describe the impact of Notch signaling on the efficacy of cancer immunotherapies. Furthermore, we summarize the results of relevant preclinical and clinical trials of Notch-targeted therapeutics and discuss the challenges in their clinical application in cancer therapy. An improved understanding of the involvement of Notch signaling in tumor immunity will open the door to new options in cancer immunotherapy treatment.

RNA editing enzymes: structure, biological functions and applications.

With the advancement of sequencing technologies and bioinformatics, over than 170 different RNA modifications have been identified. However, only a few of these modifications can lead to base pair changes, which are called RNA editing. RNA editing is a ubiquitous modification in mammalian transcriptomes and is an important co/posttranscriptional modification that plays a crucial role in various cellular processes. There are two main types of RNA editing events: adenosine to inosine (A-to-I) editing, catalyzed by ADARs on double-stranded RNA or ADATs on tRNA, and cytosine to uridine (C-to-U) editing catalyzed by APOBECs. This article provides an overview of the structure, function, and applications of RNA editing enzymes. We discuss the structural characteristics of three RNA editing enzyme families and their catalytic mechanisms in RNA editing. We also explain the biological role of RNA editing, particularly in innate immunity, cancer biogenesis, and antiviral activity. Additionally, this article describes RNA editing tools for manipulating RNA to correct disease-causing mutations, as well as the potential applications of RNA editing enzymes in the field of biotechnology and therapy.

The potential anti-tumor effect of anesthetics on cancer by regulating autophagy.

Autophagy is a conserved, cellular self-degradation system that is essential for maintaining intracellular homeostasis. Increasing evidence suggests that autophagy plays an important dual regulatory role in the development of many human diseases, such as cancer. Recent studies have shown that the autophagy process in tumor cells can be regulated by various stimuli from both intracellular and extracellular environments, including the effects of anesthesia. Anesthetics have been shown to not only have clinical anesthetic and sedative effects but also play important roles in the progression of tumors. The effects of different types of anesthetics on tumors differ. In this review, we summarize the basic information on autophagy, the regulatory function of autophagy in cancer, currently used autophagy-targeted tumor therapy, and the effects of different types of anesthetics on tumor progression. We focus on the molecular mechanisms by which anesthetics exert tumor-inhibiting effects by activating or inhibiting autophagy. Herein, we also explore the potential application of the anesthetic/autophagy system in clinical tumor treatment. These findings provide a theoretical basis for the use of anesthetics during the perioperative period to suppress tumor development and provide insights for autophagy-targeted cancer treatment and drug development.

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression.

Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.

The Role of Circular RNA Variants Generated from the NFIX Gene in Different Diseases.

Circular RNAs (circRNAs) have been identified as important regulators in different developmental processes and disease pathogenesis. The loop structure of circRNAs makes them very stable in different conditions and microenvironments. circRNAs can affect microRNA (miRNA) and RNA binding protein (RBP) activity, encode functional proteins and regulate gene transcription. Recently, two circNFIX variants derived from the same gene, the Nuclear Factor I X (NFIX) gene, were determined as participants in the pathological processes of various diseases such as heart diseases and cancers. Both circNFIX variants are exonic circular RNAs and mainly function by sponging miRNAs. In this review, we summarize the current knowledge on circRNAs, elucidate the origins and properties of two circNFIX variants, explore the roles of two circNFIX variants in different diseases, and present clinical perspectives.

Distribution and influencing factors of atmospheric nitrogen oxides (NOx) over the east coast of China in spring: Indication of the sea as a sink of the atmospheric NOx.

An integrated observation of NOx that included coastal cities and oceanic cruises covering the Qingdao coastal waters sites (QDCW) and the Yellow Sea and East China Sea sites (YECS) was conducted in spring. The average concentrations of the coastal cities, the QDCW, and the YECS were 5.4 ± 4.1, 4.2 ± 3.5, and 2.9 ± 6.8 ppb for NO while 18.5 ± 7.2, 9.4 ± 5.2, and 4.9 ± 6.4 ppb for NO2, depicting lowest levels in the open seas. Atmospheric NO and NO2 showed similar spatial variations over the seas, the stations where the air masses originated from land or nearshore regions showed higher levels, but the decisive influencing factors were not the same in the different study areas. The calculated NOx flux value in the YECS (-8.7 × 10-17 mol N cm-2) indicated that the sea surface was a net sink of atmospheric NOx.

Circulating nucleosomes as potential biomarkers for cancer diagnosis and treatment monitoring.

Nucleosomes play a crucial role in regulating gene expression through their composition and post-translational modifications. When cells die, intracellular endonucleases are activated and cleave chromatin into oligo- and mono-nucleosomes, which are then released into the body fluids. Studies have shown that the levels of nucleosomes are increased in serum and plasma in various cancer types, suggesting that analysis of circulating nucleosomes can provide an initial assessment of carcinogenesis. However, it should be noted that elevated serum nucleosome levels may not accurately diagnose certain tumor types, as increased cell death may occur in different pathological conditions. Nevertheless, detection of circulating nucleosomes and their histone modifications, along with specific tumor markers, can help diagnose certain types of cancer. Furthermore, monitoring changes in circulating nucleosome levels during chemotherapy or radiotherapy in patients with malignancies can provide valuable insights into clinical outcomes and therapeutic efficacy. The utilization of circulating nucleosomes as biomarkers is an exciting and emerging area of research, with the potential for early detection of various diseases and monitoring of treatment response. Integrating nucleosome-based biomarkers with existing ones may improve the specificity and sensitivity of current assays, offering the possibility of personalized precision medical treatment for patients.

Bismuth Ferrite-Based Lead-Free High-Entropy Piezoelectric Ceramics.

Piezoelectric ceramics, as essential components of actuators and transducers, have captured significant attention in both industrial and scientific research. The "entropy engineering" approach has been demonstrated to achieve excellent performance in lead-based materials. In this study, the "entropy engineering" approach was employed to introduce the morphotropic phase boundary (MPB) into the bismuth ferrite (BF)-based lead-free system. By employing this strategy, a serial of novel "medium to high entropy" lead-free piezoelectric ceramics were successfully synthesized, namely (1-x)BiFeO3-x(Ba0.2Sr0.2Ca0.2Bi0.2Na0.2)TiO3 (BF-xBSCBNT, x = 0.15-0.5). Our investigation systematically examined the phase structure, domain configuration, and ferroelectric/piezoelectric properties as a function of conformational entropy. Remarkable performances with a largest strain of 0.50% at 100 kV/cm, remanent polarization ∼40.07 µC/cm2, coercive field ∼74.72 kV/cm, piezoelectric coefficient ∼80 pC/N, and d33* ∼500 pm/V were achieved in BF-0.4BSCBNT ceramics. This exceptional performance can be attributed to the presence of MPB, coexisting rhombohedral and cubic phases, along with localized nanodomains. The concept of high-entropy lead-free piezoelectric ceramics in this study provides a promising strategy for the exploration and development of the next generation of lead-free piezoelectric materials.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Cancer Therapy Resistance: from Biology to Clinical Opportunity.

Mesenchymal stem cells (MSCs) are a type of stromal cells characterized by their properties of self-renewal and multi-lineage differentiation, which make them prominent in regenerative medicine. MSCs have shown significant potential for the treatment of various diseases, primarily through the paracrine effects mediated by soluble factors, specifically extracellular vesicles (EVs). MSC-EVs play a crucial role in intercellular communication by transferring various bioactive substances, including proteins, RNA, DNA, and lipids, highlighting the contribution of MSC-EVs in regulating cancer development and progression. Remarkably, increasing evidence indicates the association between MSC-EVs and resistance to various types of cancer treatments, including radiotherapy, chemotherapy, targeted therapy, immunotherapy, and endocrinotherapy. In this review, we provide an overview of the recent advancements in the biogenesis, isolation, and characterization of MSC-EVs, with an emphasis on their functions in cancer therapy resistance. The clinical applications and future prospects of MSC-EVs for mitigating cancer therapy resistance and enhancing drug delivery are also discussed. Elucidating the role and mechanism of MSC-EVs in the development of treatment resistance in cancer, as well as evaluating the clinical significance of MSC-EVs, is crucial for advancing our understanding of tumor biology. Meanwhile, inform the development of effective treatment strategies for cancer patients in the future.