A global bibliometric and visualized analysis of bacterial biofilm eradication from 2012 to 2022.

Background: To deeply explore the dynamic trends, focal points and emerging topics of bacterial biofilm eradication field and provide novel insights for prospective research endeavors, the first global bibliometric and visualized analysis of the field was employed in this study. Methods: The study meticulously curated articles and reviews concentrating on biofilm eradication from the Web of Science Core Collection (WoSCC) and identified literature published in 2012-2022 for further analysis, and the bibliometric and visualized analysis was performed to elucidate a clustering pattern in the domain with tools mainly including CiteSpace and VOSviewer. Results: 15,503 authors affiliated with 2,397 institutions spanning 96 countries or regions contributed to a corpus of 3,201 articles, containing 7,005 keywords. The USA emerged as a commanding vanguard in exploring the antibiofilm strategies and displaying pioneering initiatives within this sphere. The Chinese Academy of Sciences (CAS) emerged as the most prolific source of publications. Noteworthy among authors, Pandian Shunmugiah Karutha secured the lead in article contributions as well as co-citations while Deng Le with his team is poised to become a dominant influence in the future. Despite that, the extent of collaborative engagement across different institutions and authors appeared to fall short of its potential. Frontiers in Microbiology led the discourse by publishing a substantial body of articles and standing as the most recurrently co-cited publication. The most influential research domains encompassed "bacterial biofilm formation, "photodynamic therapy" and "phage therapy." Recent trends and forefronts concentrate on intensifying research into facilitating the shift of multiple strategies for biofilm eradication from controlled lab settings or animal studies to real-world clinical environments. Conclusion: Fundamentally, this study presents a comprehensive scrutiny and reveals that the realm of bacterial biofilm eradication is undergoing rapid evolution, with even greater expansion anticipated in the times ahead. Subsequent scholars should emphasize the augmentation of collaborative efforts and focus their energies on emerging topics, thus contributing to break through current barriers in transitioning biofilm eradication strategies from the "fundamental" stage to "practical" application.

The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders.

Vitamin D deficiency/insufficiency is a public health issue around the world. According to epidemiological studies, low vitamin D levels have been associated with an increased risk of some neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Animal models reveal that vitamin D has a variety of impacts on the synapses and circuits in the brain. A lack of vitamin D affects the expression of synaptic proteins, as well as the synthesis and metabolism of various neurotransmitters. Depending on where vitamin D receptors (VDRs) are expressed, vitamin D may also regulate certain neuronal circuits through the endocannabinoid signaling, mTOR pathway and oxytocin signaling. While inconsistently, some data suggest that vitamin D supplementation may be able to reduce the core symptoms of ASD and ADHD. This review emphasizes vitamin D's role in the synaptic and circuit mechanisms of neurodevelopmental disorders including ASD and ADHD. Future application of vitamin D in these disorders will depend on both basic research and clinical studies, in order to make the transition from the bench to the bedside.

Network Analysis of ADHD Symptoms and Cognitive Profiles in Children.

Purpose: Although many studies have reported the cognitive profiles in attention-deficit/hyperactivity disorder (ADHD), the interactions between ADHD symptoms and the patients' cognitive profiles have not been carefully examined through the network analysis. Here, in this study, we systematically analyzed the ADHD patents' symptoms and cognitive profiles, and identified a set of interactions between ADHD symptoms and cognitive domains using the network approach. Patients and Methods: A total of 146 children with ADHD, 6 to 15 years of age, were included in the study. All participants were assessed by the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) test. The patients' ADHD symptoms were evaluated by the Vanderbilt ADHD parent and teacher rating scales. GraphPad Prism 9.1.1 software was used for descriptive statistics and R 4.2.2 was used for network model construction. Results: The ADHD children in our sample showed lower scores for full scale intelligence quotient (FSIQ), verbal comprehension index (VCI), processing speed index (PSI) and working memory index (WMI). Among all the ADHD core symptoms and comorbid symptoms, the academic ability, inattention symptoms and mood disorder showed direct interaction with the cognitive domains of WISC-IV. In addition, oppositional defiant of the ADHD comorbid symptoms, and perceptual reasoning of the cognitive domains exhibited the highest strength centrality in the ADHD-Cognition network based on parent ratings. Classroom behaviors of the ADHD functional impairment, and verbal comprehension of the cognitive domains exhibited the highest strength centrality in the network based on teacher ratings. Conclusion: We highlighted the importance of considering the interactions between the ADHD symptoms and cognitive properties when designing the intervention plans for the ADHD children.

Stratifying ASD and characterizing the functional connectivity of subtypes in resting-state fMRI.

BACKGROUND: Although stratifying autism spectrum disorder (ASD) into different subtypes is a common effort in the research field, few papers have characterized the functional connectivity alterations of ASD subgroups classified by their clinical presentations. METHODS: This is a case-control rs-fMRI study, based on large samples of open database (Autism Brain Imaging Data Exchange, ABIDE). The rs-MRI data from n = 415 ASD patients (males n = 357), and n = 574 typical development (TD) controls (males n = 410) were included. Clinical features of ASD were extracted and classified using data from each patient's Autism Diagnostic Interview-Revised (ADI-R) evaluation. Each subtype of ASD was characterized by local functional connectivity using regional homogeneity (ReHo) for assessment, remote functional connectivity using voxel-mirrored homotopic connectivity (VMHC) for assessment, the whole-brain functional connectivity, and graph theoretical features. These identified imaging properties from each subtype were integrated to create a machine learning model for classifying ASD patients into the subtypes based on their rs-fMRI data, and an independent dataset was used to validate the model. RESULTS: All ASD participants were classified into Cluster-1 (patients with more severe impairment) and Cluster-2 (patients with moderate impairment) according to the dimensional scores of ADI-R. When compared to the TD group, Cluster-1 demonstrated increased local connection and decreased remote connectivity, and widespread hyper- and hypo-connectivity variations in the whole-brain functional connectivity. Cluster-2 was quite similar to the TD group in both local and remote connectivity. But at the level of whole-brain functional connectivity, the MCC-related connections were specifically impaired in Cluster-2. These properties of functional connectivity were fused to build a machine learning model, which achieved ∼75% for identifying ASD subtypes (Cluster-1 accuracy = 81.75%; Cluster-2 accuracy = 76.48%). CONCLUSIONS: The stratification of ASD by clinical presentations can help to minimize disease heterogeneity and highlight the distinguished properties of brain connectivity in ASD subtypes.

Activity-Dependent Differential Regulation of Auts2 Isoforms In Vitro and In Vivo.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of unknown cause, although one hypothesis suggests a potential imbalance between excitation and inhibition that leads to changes in neuronal activity and a disturbance in the brain network. However, the mechanisms through which neuronal activity contributes to the development of ASD remain largely unexplained. In this study, we described that neuronal activity at the transcriptional and translational levels regulated the expression of Auts2 isoforms. The prolonged stimulation of cultured cortical neurons significantly reduced the auts2 transcripts, accompanied by the decrease of FL-Auts2 protein, as well as one of the short isoforms (S-Auts2 var.1). Blocking neuronal activity increased the number of auts2 transcripts but not protein levels. Furthermore, blocking the NMDA receptors during stimulation could partially restore the FL-Auts2 and S-Auts2 var.1 at protein level, but not at mRNA level. Finally, Auts2 expression in the hippocampus was reduced in mice exposed to an enriched environment, a behavior paradigm designed to increase the brain activity through abundant sensory and social stimulations. Thus, our study revealed a novel regulatory effect of neuronal activity on the transcription and translation of ASD-risk gene auts2.

MCU-dependent mitochondrial calcium uptake-induced mitophagy contributes to apelin-13-stimulated VSMCs proliferation.

Apelin is an endogenous ligand of the G protein-coupled receptor APJ. Both apelin and APJ receptors, which are expressed in vascular smooth muscle cells (VSMCs), play important roles in the cardiovascular system. Our previous studies researches indicated that mitophagy mediated apelin-13-induced VSMCs proliferation. However, little is known about how apelin-13 regulates mitophagy to participate in VSMC proliferation. The results of the present study demonstrated that mitochondrial calcium uniporter (MCU) uptake-dependent mitochondrial calcium-induced mitophagy is involved in apelin-13-induced VSMCs proliferation. Apelin-13 promoted the expression of MCU which increases mitochondrial calcium uptake. Apelin-13-induced MCU-dependent mitochondrial calcium uptake further increased mitochondrial ROS (mtROS) concentrations and promoted mitophagy, which can be evidenced through the upregulation of the Dynamin-related protein 1(Drp1), PTEN-induced kinase 1 (PINK1), and Parkin. The clearance of mtROS by Mito-TEMPO significantly reversed apelin-13-induced mitophagy. Moreover, both the Drp1 inhibitor mdivi-1 and siRNA-Drp1 inhibited apelin-13-induced mitophagy. Furthermore, the APJ receptor antagonist F13A, MCU inhibitor Ru360, mitochondria-targeted antioxidant Mito-TEMPO, Drp1 inhibitor Mdivi-1, siRNA-Drp1, siRNA-PINK1, and siRNA-Parkin inhibited the proliferation of VSMCs induced by apelin-13. In ApoE-/- mice, intraperitoneal administration of apelin-13 induced the expression of MCU, Drp1, PINK1, Parkin, and α-SMA and increased atherosclerotic plaque lesions. However, F13A and Ru360 decreased the expression of MCU, Drp1, PINK1, Parkin, and α-SMA and reduced atherosclerotic plaque lesions in ApoE-/- mice injected with apelin-13. Collectively, our results demonstrate that MCU-dependent mitochondrial calcium uptake-induced mitophagy is involved in apelin-13-stimulated VSMCs proliferation.

Apelin/APJ signaling activates autophagy to promote human lung adenocarcinoma cell migration.

AIMS: Beclin1(BECN1) is known as an autophagy-related protein and the expression is promoted by apelin in lung adenocarcinoma cells, suggesting that apelin activates autophagy in lung adenocarcinoma. However, the functions of apelin-induced autophagy in lung adenocarcinoma tumorigenesis and deterioration are still unknown. Thus, this study aims to investigate the effects of apelin-induced autophagy on lung adenocarcinoma tumorigenesis and deterioration. MAIN METHODS: Protein expression of exogenous genes were detected by Western blotting analysis. Lung adenocarcinoma cell migration was assessed with cell migration assays. Autophagy was measured with quantification of GFP-LC3 or RFP-GFP-LC3 puncta using fluorescence microscopy in cells by an observed blinded to experimental condition and by western blot analysis of LC3 and p62 in cell lysates as well as autophagy flux. Immunofluorescence staining was performed in human lung adenocarcinoma A549 cells with p-cofilin antibody. The proteins expression in cancer specimens were examined with immunohistochemistry. KEY FINDINGS: Here, we reveal that apelin induces autophagy activation in lung adenocarcinoma. Apelin/APJ regulates BECN1 transcription via HIF1A. Apelin/APJ-activated autophagy promotes lung adenocarcinoma cell migration. Moreover, treatment with autophagy inhibitors significantly decreases apelin/APJ-induced lung adenocarcinoma cell migration. Evaluation of patient samples of lung adenocarcinoma reveals an association between APJ with BECN1 expression and a poor prognosis. SIGNIFICANCE: Our studies demonstrate that apelin-induced autophagy promotes lung adenocarcinoma cell migration which suggests a potential therapeutic target for lung adenocarcinoma.

Mitochondrial iron metabolism and its role in diseases.

Iron is one of the most important elements for life, but excess iron is toxic. Intracellularly, mitochondria are the center of iron utilization requiring sufficient amounts to maintain normal physiologic function. Accordingly, disruption of iron homeostasis could seriously impact mitochondrial function leading to impaired energy state and potential disease development. In this review, we discuss mechanisms of iron metabolism including transport, processing, heme synthesis, iron-sulfur cluster biogenesis and storage. We highlight the vital role of mitochondrial iron in pathologic states including neurodegenerative disorders and sideroblastic anemia.

Mitochondrial unfolded protein response: An emerging pathway in human diseases.

Mitochondrial unfolded protein response (UPRmt) is a mitochondria stress response, which the transcriptional activation programs of mitochondrial chaperone proteins and proteases are initiated to maintain proteostasis in mitochondria. Additionally, the activation of UPRmt delays aging and extends lifespan by maintaining mitochondrial proteostasis. Growing evidences suggests that UPRmt plays an important role in diverse human diseases, especially ageing-related diseases. Therefore, this review focuses on the role of UPRmt in ageing and ageing-related neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease. The activation of UPRmt and the high expression of UPRmt components contribute to longevity extension. The activation of UPRmt may ameliorate Alzheimer's disease, Parkinson's disease and Huntington's disease. Besides, UPRmt is also involved in the occurrence and development of cancers and heart diseases. UPRmt contributes to the growth, invasive and metastasis of cancers. UPRmt has paradoxical roles in heart diseases. UPRmt not only protects against heart damage, but may sometimes aggravates the development of heart diseases. Considering the pleiotropic actions of UPRmt system, targeting UPRmt pathway may be a potent therapeutic avenue for neurodegenerative diseases, cancers and heart diseases.

Endoplasmic reticulum stress and focused drug discovery in cardiovascular disease.

Endoplasmic reticulum (ER) is an intracellular membranous organelle involved in the synthesis, folding, maturation and post-translation modification of secretory and transmembrane proteins. Therefore, ER is closely related to the maintenance of intracellular homeostasis and the good balance between health and diseases. Endoplasmic reticulum stress (ERS) occurs when unfolded/misfolded proteins accumulate after disturbance of ER environment. In response to ERS, cells trigger an adaptive response called the Unfolded protein response (UPR), which helps cells cope with the stress. In recent years, a large number of studies show that ERS can aggravate cardiovascular diseases. ERS-related proteins expression in cardiovascular diseases is on the rise. Therefore, down-regulation of ERS is critical for alleviating symptoms of cardiovascular diseases, which may be used in the near future to treat cardiovascular diseases. This article reviews the relationship between ERS and cardiovascular diseases and drugs that inhibit ERS. Furthermore, we detail the role of ERS inhibitors in the treatment of cardiovascular disease. Drugs that inhibit ERS are considered as promising strategies for the treatment of cardiovascular diseases.

Warburg effect is involved in apelin-13-induced human aortic vascular smooth muscle cells proliferation.

Apelin is the endogenous ligand for the G protein-coupled receptor APJ. Both apelin and APJ receptor are distributed in vascular smooth muscle cells (VSMCs) and play important roles in the cardiovascular system. Our previous reports have indicated that apelin-13 promoted the proliferation of VSMCs, but its exact mechanism remains to be further explored. The results of the present study demonstrated that the Warburg effect plays a pivotal role in apelin-13-induced human aortic vascular smooth muscle cells (HA-VSMCs) proliferation. Apelin-13 promoted the expression of glucose transporter type 1 (GLUT1), pyruvate kinase 2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter 1 (MCT1), and monocarboxylate transporter 4 (MCT4) in a dose- and time-dependent manner. Moreover, apelin-13 increased the extracellular, intracellular lactate level, and decreased adenosine triphosphate level in HA-VSMCs. Furthermore, siRNA-PKM2 reversed extracellular and intracellular lactate generation and inhibited the proliferation of HA-VSMCs induced by apelin-13. Downregulation of LDHA also significantly prevented extracellular and intracellular lactate generation and inhibited the proliferation of HA-VSMCs induced by apelin-13. Taken together, our results demonstrated a novel mechanism for HA-VSMCs proliferation induced by apelin-13 via Warburg effect.

PINK1/Parkin-mediated mitophagy promotes apelin-13-induced vascular smooth muscle cell proliferation by AMPKα and exacerbates atherosclerotic lesions.

Aberrant proliferation of vascular smooth muscle cells (VSMC) is a critical contributor to the pathogenesis of atherosclerosis (AS). Our previous studies have demonstrated that apelin-13/APJ confers a proliferative response in VSMC, however, its underlying mechanism remains elusive. In this study, we aimed to investigate the role of mitophagy in apelin-13-induced VSMC proliferation and atherosclerotic lesions in apolipoprotein E knockout (ApoE-/-) mice. Apelin-13 enhances human aortic VSMC proliferation and proliferative regulator proliferating cell nuclear antigen expression in dose and time-dependent manner, while is abolished by APJ antagonist F13A. We observe the engulfment of damage mitochondria by autophagosomes (mitophagy) of human aortic VSMC in apelin-13 stimulation. Mechanistically, apelin-13 increases p-AMPKα and promotes mitophagic activity such as the LC3I to LC3II ratio, the increase of Beclin-1 level and the decrease of p62 level. Importantly, the expressions of PINK1, Parkin, VDAC1, and Tom20 are induced by apelin-13. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. Human aortic VSMC transfected with AMPKα, PINK1, or Parkin and subjected to apelin-13 impairs mitophagy and prevents proliferation. Additional, apelin-13 not only increases the expression of Drp1 but also reduces the expressions of Mfn1, Mfn2, and OPA1. Remarkably, the mitochondrial division inhibitor-1(Mdivi-1), the pharmacological inhibition of Drp1, attenuates human aortic VSMC proliferation. Treatment of ApoE-/- mice with apelin-13 accelerates atherosclerotic lesions, increases p-AMPKα and mitophagy in aortic wall in vivo. Finally, PINK1-/- mutant mice with apelin-13 attenuates atherosclerotic lesions along with defective in mitophagy. PINK1/Parkin-mediated mitophagy promotes apelin-13-evoked human aortic VSMC proliferation by activating p-AMPKα and exacerbates the progression of atherosclerotic lesions.

Apelin/APJ system: A novel promising target for anti-aging intervention.

Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is widely expressed in various organs. Recent research has indicated that the Apelin/APJ system plays an important role in aging. Apelin and APJ receptor expression are down-regulated with increasing age. In murine models, Apelin and APJ knockouts exhibit accelerated senescence whereas Apelin-restoration results in enhanced vigor and rejuvenated behavioral and circadian phenotypes. Furthermore, aged Apelin knockout mice develop progressive impairment of cardiac contractility associated with systolic dysfunction. Apelin is crucial to maintain cardiac contractility in aging. Moreover, the Apelin/APJ system appears to be involved in regulation of renin-angiotensin-aldosterone system (RAAS), apoptosis, inflammation and oxidative stress which promotes aging. Likewise, the Apelin/APJ system regulates autophagy, stem cells and the sirtuin family thus contributing to anti-aging. In this review, we describe the relationship between Apelin/APJ system and aging. We elaborate on the role of the Apelin/APJ system in aging stimulators, aging inhibitors and age-related diseases such as obesity, diabetes and cardiovascular disease. We conclude that Apelin/APJ system might become a novel promising therapeutic target for anti-aging.