SAN: Mitigating spatial covariance heterogeneity in cortical thickness data collected from multiple scanners or sites.

In neuroimaging studies, combining data collected from multiple study sites or scanners is becoming common to increase the reproducibility of scientific discoveries. At the same time, unwanted variations arise by using different scanners (inter-scanner biases), which need to be corrected before downstream analyses to facilitate replicable research and prevent spurious findings. While statistical harmonization methods such as ComBat have become popular in mitigating inter-scanner biases in neuroimaging, recent methodological advances have shown that harmonizing heterogeneous covariances results in higher data quality. In vertex-level cortical thickness data, heterogeneity in spatial autocorrelation is a critical factor that affects covariance heterogeneity. Our work proposes a new statistical harmonization method called spatial autocorrelation normalization (SAN) that preserves homogeneous covariance vertex-level cortical thickness data across different scanners. We use an explicit Gaussian process to characterize scanner-invariant and scanner-specific variations to reconstruct spatially homogeneous data across scanners. SAN is computationally feasible, and it easily allows the integration of existing harmonization methods. We demonstrate the utility of the proposed method using cortical thickness data from the Social Processes Initiative in the Neurobiology of the Schizophrenia(s) (SPINS) study. SAN is publicly available as an R package.

Aldehyde dehydrogenase 1 family: A potential molecule target for diseases.

Aldehyde dehydrogenase 1 (ALDH1), a crucial aldehyde metabolizing enzyme, has six family members. The ALDH1 family is expressed in various tissues, with a significant presence in the liver. It plays a momentous role in several pathophysiological processes, including aldehyde detoxification, oxidative stress, and lipid peroxidation. Acetaldehyde detoxification is the fundamental function of the ALDH1 family in participating in vital pathological mechanisms. The ALDH1 family can catalyze retinal to retinoic acid (RA) that is a hormone-signaling molecule and plays a vital role in the development and adult tissues. Furthermore, there is a need for further and broader research on the role of the ALDH1 family as a signaling molecule. The ALDH1 family is widely recognized as a cancer stem cell (CSC) marker and plays a significant role in the proliferation, invasion, metastasis, prognosis, and drug resistance of cancer. The ALDH1 family also participates in other human diseases, such as neurodegenerative diseases, osteoarthritis, diabetes, and atherosclerosis. It can inhibit disease progression by inhibiting/promoting the expression/activity of the ALDH1 family. In this review, we comprehensively analyze the tissue distribution, and functions of the ALDH1 family. Additionally, we review the involvement of the ALDH1 family in diseases, focusing on the underlying pathological mechanisms and briefly talk about the current status and development of ALDH1 family inhibitors. The ALDH1 family presents new possibilities for treating diseases, with both its upstream and downstream pathways serving as promising targets for therapeutic intervention. This offers fresh perspectives for drug development in the field of disease research.

Predictors of the Rapid Progression in Prodromal Parkinson's Disease: A Longitudinal Follow-Up Study.

INTRODUCTION: Parkinson's disease (PD) is characterized by a prodromal phase preceding the onset of classic motor symptoms. The duration and clinical manifestations of prodromal PD vary widely, indicating underlying heterogeneity within this stage. This discrepancy prompts the question of whether specific factors contribute to the divergent rates of progression in prodromal PD. METHODS: This study included prodromal PD patients from the Parkinson's progression marker initiative. They were followed up to assess the disease progression. The data collected during the follow-up period were analyzed to identify potential predictors of rapid disease progression in prodromal PD. RESULTS: In this study, 61 individuals with prodromal PD were enrolled. Among them, 43 patients presented with both RBD and hyposmia, 17 had hyposmia alone, and 1 had RBD alone at baseline. 13 (21.3%) prodromal PD participants exhibited rapid disease progression, with two of these cases advancing to non-neurological diseases. Significant differences were observed between the rapid progression group and no rapid progression group in terms of MDS-UPDRS II score and UPSIT score. Longitudinal analysis showed a significant increase in the MDS-UPDRS III score and MDS-UPDRS total score in the rapid progression group. Regression analyses identified the MDS-UPDRS II score and UPSIT score as predictors of rapid disease progression in prodromal PD. CONCLUSION: Our study findings suggest that the MDS-UPDRS II score and UPSIT score may serve as clinical markers associated with rapid disease progression. Further research and development of precise biomarkers and advanced assessment methods are needed to enhance our understanding of prodromal PD and its progression patterns.

Glycogen-binding protein STBD1: Molecule and role in pathophysiology.

Starch-binding domain-containing protein 1 (STBD1) is a glycogen-binding protein discovered in skeletal muscle gene differential expression that is pivotal to cellular energy metabolism. Recent studies have indicated that STBD1 is involved in many physiological processes, such as glycophagy, glycogen accumulation, and lipid droplet formation. Moreover, dysregulation of STBD1 causes multiple diseases, including cardiovascular disease, metabolic disease, and even cancer. Deletions and/or mutations in STBD1 promote tumorigenesis. Therefore, STBD1 has garnered considerable interest in the pathology community. In this review, we first summarized the current understanding of STBD1, including its structure, subcellular localization, tissue distribution, and biological functions. Next, we examined the roles and molecular mechanisms of STBD1 in related diseases. Based on available research, we discussed the novel function and future of STBD1, including its potential application as a therapeutic target in glycogen-related diseases. Given the significance of STBD1 in energy metabolism, an in-depth understanding of the protein is crucial for understanding physiological processes and developing therapeutic strategies for related diseases.

Multifaceted functions of RPS27a: An unconventional ribosomal protein.

The ribosomal protein S27a (RPS27a) is cleaved from the fusion protein ubiquitin-RPS27a (Ub-RPS27a). Generally, Ub and RPS27a are coexpressed as a fusion protein but function independently after Ub is cleaved from RPS27a by a deubiquitinating enzyme. As an RP, RPS27a assembles into ribosomes, but it also functions independently of ribosomes. RPS27a is involved in the development and poor prognosis of various cancers, such as colorectal cancer, liver cancer, chronic myeloid leukemia, and renal carcinoma, and is associated with poor prognosis. Notably, the murine double minute 2/P53 axis is a major pathway through which RPS27a regulates cancer development. Moreover, RPS27a maintains sperm motility, regulates winged aphid indirect flight muscle degeneration, and facilitates plant growth. Additionally, RPS27a is a metalloprotein and mercury (Hg) biomarker. In the present review, we described the origin, structure, and biological functions of RPS27a.

Elabela-apelin-12, 17, 36/APJ system promotes platelet aggregation and thrombosis via activating the PANX1-P2X7 signaling pathway.

The elabela-apelin/angiotensin domain type 1 receptor-associated protein (APJ) system is an important regulator in certain thrombosis-related diseases such as atherosclerosis, myocardial infarction, and cerebral infarction. Our previous reports have revealed that apelin exacerbates atherosclerotic lesions. However, the relationship between the elabela-apelin/APJ system and platelet aggregation and atherothrombosis is unclear. The results of the present study demonstrate that elabela and other endogenous ligands such as apelin-12, -17, and -36 induce platelet aggregation and thrombosis by activating the pannexin1(PANX1)-P2X7 signaling pathway. Interestingly, the diuretic, spironolactone, a novel PANX1 inhibitor, alleviated elabela- and apelin isoforms-induced platelet aggregation and thrombosis. Significantly, two potential antithrombotic drugs were screened out by targeting APJ receptors, including the anti-HIV ancillary drug cobicistat and the traditional Chinese medicine monomer Schisandrin A. Both cobicistat and Schisandrin A abolished the effects of elabela and apelin isoforms on platelet aggregation, thrombosis, and cerebral infarction. In addition, cobicistat significantly attenuated thrombosis in a ponatinib-induced zebrafish trunk model. Overall, the elabela-apelin/APJ axis mediated platelet aggregation and thrombosis via the PANX1-P2X7 signaling pathway in vitro and in vivo. Blocking the APJ receptor with cobicistat/Schisandrin A or inhibiting PANX1 with spironolactone may provide novel therapeutic strategies against thrombosis.

A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases.

Mammalian autophagy-related protein Atg8, including the LC3 subfamily and GABARAP subfamily. Atg8 proteins play a vital role in autophagy initiation, autophagosome formation and transport, and autophagy-lysosome fusion. GABARAP subfamily proteins (GABARAPs) share a high degree of homology with LC3 family proteins, and their unique roles are often overlooked. GABARAPs are as indispensable as LC3 in autophagy. Deletion of GABARAPs fails autophagy flux induction and autophagy lysosomal fusion, which leads to the failure of autophagy. GABARAPs are also involved in the transport of selective autophagy receptors. They are engaged in various particular autophagy processes, including mitochondrial autophagy, endoplasmic reticulum autophagy, Golgi autophagy, centrosome autophagy, and dorphagy. Furthermore, GABARAPs are closely related to the transport and delivery of the inhibitory neurotransmitter γ-GABAA and the angiotensin II AT1 receptor (AT1R), tumor growth, metastasis, and prognosis. GABARAPs also have been confirmed to be involved in various diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. In order to better understand the role and therapeutic potential of GABARAPs, this article comprehensively reviews the autophagic and non-autophagic functions of GABARAPs, as well as the research progress of the role and mechanism of GABARAPs in cancer, cardiovascular diseases and neurodegenerative diseases. It emphasizes the significance of GABARAPs in the clinical prevention and treatment of diseases, and may provide new therapeutic ideas and targets for human diseases. GABARAP and GABARAPL1 in the serum of cancer patients are positively correlated with the prognosis of patients, which can be used as a clinical biomarker, predictor and potential therapeutic target. GABARAP family proteins: autophagy and non-autophagy related functions in diseases. By Figdraw ( https://www.figdraw.com ).

Apelin/APJ system: an emerging therapeutic target for neurological diseases.

Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is extensively expressed in various systems, especially the nervous system. This article reviews the role of apelin/APJ system in neurological diseases. In detail, apelin/APJ system can relieve acute brain injury including subarachnoid hemorrhage, traumatic brain injury, and ischemic stroke. Also, apelin/APJ system has therapeutic effects on chronic neurodegenerative disease models, involving the regulation of neurotrophic factors, neuroendocrine, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy. In addition, through different routes of administration, apelin/APJ system has a biphasic effect on depression, epilepsy, and pain. However, apelin/APJ system exacerbates the proliferation and invasion of glioblastoma. Thus, apelin/APJ system is expected to be a therapeutic target for the treatment of nervous system diseases.

Lysosome-targeted fluorescent probes: Design mechanism and biological applications.

As an integral organelle in the eukaryote, the lysosome is the degradation center and metabolic signal center in living cells, and partakes in significant physiological processes such as autophagy, cell death and cellular senescence. Fluorescent probe has become a favorite tool for studying organelles and their chemical microenvironments because of its high specificity and non-destructive merits. Over recent years, it has been reported that increasingly new lysosome-targeted probes play a major role in the diagnosis and monitor of diseases, in particular cancer and neurodegenerative diseases. In order to deepen the relevant research on lysosome, it is challenging and inevitability to design novel lysosomal targeting probes. This review first introduces the concepts of lysosome and its closely related biological activities, and then introduces the fluorescent probes for lysosome in detail according to different detection targets, including targeting mechanism, biological imaging, and application in diseases. Finally, we summarize the specific challenges and discuss the future development direction facing the current lysosome-targeted fluorescent probes. We hope that this review can help biologists grasp the application of fluorescent probes and broaden the research ideas of researchers targeting fluorescent probes so as to design more accurate and functional probes for application in diseases.

Multiple functions of CALCOCO family proteins in selective autophagy.

Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through the activity of selective autophagy receptors. CALCOCO family proteins are the newly found selective autophagy receptors, which include calcium binding and coiled-coil domain 1 (CALCOCO1), calcium binding and coiled-coil domain 2/nuclear domain 10 protein 52 (CALCOCO2/NDP52), and calcium binding and coiled-coil domain 3/Tax1-binding protein 1 (CALCOCO3/TAX1BP1). Specifically, CALCOCO1 can be recruited to endoplasmic reticulum (ER) and Golgi to mediate selective ER-phagy and Golgiphagy. CALCOCO2 and CALCOCO3, which are two essential cargo receptors, can mediate mitophagy and xenophagy through interacting with autophagy-related-8/microtubule-associated protein 1 light chain 3 (ATG8/LC3) on the growing autophagosome, and binding ubiquitin for cargo recruitment. Considering the significance of these proteins in selective autophagy, we review the structures, distribution, posttranslational modifications, and phylogenetic analysis of CALCOCO family proteins and their roles in different selective autophagy.

Roles of apelin/APJ system in cancer: Biomarker, predictor, and emerging therapeutic target.

Cancer is a disease that seriously endangers human health and is mainly characterized by a high metastasis rate, a high recurrence rate, and a high mortality rate. The treatment of cancer has always been an important research direction of scientific research. A number of studies have shown that the apelin/APJ system is involved in the development and poor prognosis of a variety of cancers, such as lung cancer, liver cancer, cholangiocarcinoma, breast cancer, glioblastoma, prostate cancer, ovarian cancer, and so on. Accumulating evidence has also shown that the apelin/APJ system acts as a biomarker and predictor of postoperative effects in multiple cancers, which can also affect the tumor microenvironment and the efficacy of cancer immunotherapy. Considering that the apelin/APJ system may be a potential target for cancer treatment, it is of great significance for the study of new cancer treatment targets. To better understand the role of the apelin/APJ system on the occurrence and development of cancer, this article reviews the role of the apelin/APJ system in the occurrence and development of various cancers, angiogenesis, tumor stem cells, tumor microenvironment, drug resistance, poor prognosis, and the research progress of related anticancer drugs.

Apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy.

Cardiac hypertrophy is a leading cause of cardiac morbidity and mortality worldwide. Apelin is the endogenous ligand for the G protein-coupled receptor, APJ. Previously, we have revealed that apelin-13 can induce cardiomyocyte hypertrophy by activating the autophagy pathway. However, the precise mechanism through which apelin-13 regulates reticulophagy to participate in cardiomyocyte hypertrophy remains unclear. Herein, we observed that apelin-13-induced cardiomyocyte hypertrophy by activating FAM134B-dependent reticulophagy via the Pannexin-1/P2X7 signal pathway. Furthermore, we found that apelin-13 stimulated the opening of Pannexin-1 hemichannel and increased extracellular ATP (eATP) levels, which activated the P2X7 purinergic receptor. Activation of the Pannexin-1/eATP/P2X7 axis subsequently led to FAM134B-dependent reticulophagy. Moreover, inhibition of the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy reversed apelin-13-induced cardiomyocyte hypertrophy. Based on our present findings, apelin-13/APJ induces cardiomyocyte hypertrophy by activating the Pannexin-1/P2X7 axis and FAM134B-dependent reticulophagy.

The biological effects of geomagnetic field exhibit an important potential for cancer and vascular diseases.

Xu et al. recently demonstrated that cryptochrome 4 (CRY4) protein, as a light-dependent magnetic receptor, can sense geomagnetic fields to guide night-migratory songbirds' navigation and evolution by the formation of composite radical pairs and electron transport. We aim to comment on CRY4 through radical pairs and electron transport for magnetic sensitive in night-migratory songbirds' migration and evolution. Additionally, we find that the role of magnetic fields is deeply concerning to the scientific community and very enlightening for the diagnosis and treatment of cancer and vascular disease. We believe that this commentary makes a significant contribution to the literature because it elaborates on the importance of the geomagnetic field to night-migratory songbirds and extends the diagnostic and therapeutic value to cancer and vascular disease.

The role of metal ions in the Golgi apparatus.

The Golgi apparatus is a membrane-bound organelle that functions as a central role in the secretory pathway. Since the discovery of the Golgi apparatus, its structure and function have attracted ever-increasing attention from researchers. Recently, it has been demonstrated that metal ions are necessary for the Golgi apparatus to maintain its proper structure and functions. Given that metal ions play an important role in various biological processes, their abnormal homeostasis is related to many diseases. Therefore, in this paper, we reviewed the uptake and release mechanisms of the Golgi apparatus Ca2+ , Cu, and Zn2+ . Furthermore, we describe the diseases associated with Golgi apparatus Ca2+ , Cu, and Zn2+ imbalance.

Platelet-derived respiratory-competent mitochondria transfer to mesenchymal stem cells to promote wound healing via metabolic reprogramming.

Mitochondria regulate intracellular metabolism and are also involved in intercellular transfer in vitro and in vivo, thereby affecting the function of adjacent cells. Mitochondria can also be transferred to various differentiated cells to improve their respiratory function, ATP production, as well as protect damaged cells from apoptosis. Both in vivo and in vitro, mitochondria can be transferred from one cell to another to regulate cellular metabolism under physiological or pathophysiological conditions, referred to as "mitochondrial translocation". Mitochondrial translocation is associated in various situations such as repairing damaged cells, promoting cancer progression and enhancing chemoresistance. Platelets contain mitochondria that promote energy metabolism and various growth factors, thus playing an important role in pathophysiological processes such as thrombosis, hemostasis, inflammation and wound healing. Current studies suggest that mesenchymal stem cells (MSCs) can communicate with their microenvironment through bidirectional alternation of mitochondria to improve their wound healing capacity. Platelets or platelet-containing preparations such as platelet-rich plasma (PRP) can stimulate the proliferation and pro-angiogenic properties of MSCs under oxidative stress to enhance their survival. Recent studies by Levoux et al. have shown that activated platelet-derived mitochondria have the respiratory capacity to translocate to MSCs and stimulate the pro-angiogenic properties of MSCs through metabolic reprogramming, thereby promoting angiogenesis and wound healing. The mechanism of mitochondrial internalization of cells and energy metabolism is a new example of mitochondrial translocation altering somatic cell behavior and viability. Therefore, we aim to comment the mechanisms of platelet mitochondrial translocation and metabolic reprogramming of MSCs, suggesting that platelets or platelet-containing preparations such as platelet-rich plasma (PRP) may provide a practical guide for tissue injury treatment.

Therapeutic potential of traditional Chinese medicine in atherosclerosis: A review.

Atherosclerosis is the onset of endothelial cell damage and is characterized by abnormal accumulation of fibrinogen and lipid in large and middle arteries. Recent researches indicate that traditional Chinese medicine including Notoginseng Radix et Rhizoma, Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Fructus Crataegi, Glycyrrhizae Radix et Rhizoma, Polygoni Multiflori Radix, Fructus Lycii, and Coptidis Rhizoma have therapeutic effects on atherosclerosis. Furthermore, the pharmacological roles of these kinds of traditional Chinese medicine in atherosclerosis refer to endothelial function influences, cell proliferation and migration, platelet aggregation, thrombus formation, oxidative stress, inflammation, angiogenesis, apoptosis, autophagy, lipid metabolism, and the gut microbiome. Traditional Chinese medicine may serve as potential and effective anti-atherosclerosis drugs. However, a critical study has shown that Notoginseng Radix et Rhizoma may also have toxic effects including pustules, fever, and elevate circulating neutrophil count. Further high-quality studies are still required to determine the clinical safety and efficacy of traditional Chinese medicine and its active ingredients.

Targeting signal pathways triggered by cyclic peptides in cancer: Current trends and future challenges.

Cancer is a global health issue that origins thousands of deaths annually worldwide. Cyclic peptides are polypeptide chains which are formed by cyclic sequence of amide bonds between proteinogenic or non-proteinogenic amino acids. Numerous evidences indicate that cyclic peptides are implicated with the occurrence and development of cancer. This review presents the current knowledge about the role of cyclic peptides in cancer, such as liver cancer, colorectal cancer, ovarian cancer, breast cancer as well as prostate cancer. Specifically, the precise molecular mechanisms between cyclic peptides and cancer are elaborated. Some cyclic peptides from nature and synthesis prevent the occurrence and development of cancer. However, some other cyclic peptides including endothelin-1, urotensinⅡand melanin-concentrating hormone deteriorate the pathogenesis of cancer. Given the pleiotropic actions of cyclic peptides, the identification and development of cyclic peptides and their derivates as drug may be a potent therapeutic strategy for cancer.

Mitochondrial unfolded protein response: A novel pathway in metabolism and immunity.

Mitochondrial unfolded protein response (mitoUPR) is a mitochondria stress response to maintain mitochondrial proteostasis during stress. Increasing evidence suggests that mitoUPR participates in diverse physiological processes especially metabolism and immunity. Although mitoUPR regulates metabolism in many aspects, it is mainly reflected in the regulation of energy metabolism. During stress, mitoUPR alters energy metabolism via suppressing oxidative phosphorylation (OXPHOS) or increasing glycolysis. MitoUPR also alters energy metabolism and regulates diverse metabolic diseases such as diabetes, cancers, fatty liver and obesity. In addition, mitoUPR also participates in immune process during stress. MitoUPR can induce innate immune response during various infections and may regulate inflammatory response during diverse inflammations. Considering the pleiotropic actions of mitoUPR, mitoUPR may supply diverse therapeutic targets for metabolic diseases and immune diseases.

M6 A modification: A mechanism for protecting hematopoietic development in mammals.

N6 -methyladenosine (m6 A) is one of the most common internal modifications in messenger RNA, which is necessary for cell physiological activities. A recent study shows that during mammalian hematopoietic development, loss of m6 A modification leads to the aberrant production of double-stranded RNA, which results in the abnormal activation of innate immune response, and ultimately leads to hematopoietic failure. Accordingly, m6 A modification provide us an attractive direction for us to understand mammalian hematopoietic development and innate immune response.

Apelin/APJ system: an emerging therapeutic target for respiratory diseases.

Apelin is an endogenous ligand of G protein-coupled receptor APJ. It is extensively expressed in many tissues such as heart, liver, and kidney, especially in lung tissue. A growing body of evidence suggests that apelin/APJ system is closely related to the development of respiratory diseases. Therefore, in this review, we focus on the role of apelin/APJ system in respiratory diseases, including pulmonary arterial hypertension (PAH), pulmonary embolism (PE), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), obstructive sleep apnoea syndrome (OSAS), non-small cell lung cancer (NSCLC), pulmonary edema, asthma, and chronic obstructive pulmonary diseases. In detail, apelin/APJ system attenuates PAH by activating AMPK-KLF2-eNOS-NO signaling and miR424/503-FGF axis. Also, apelin protects against ALI/ARDS by reducing mitochondrial ROS-triggered oxidative damage, mitochondria apoptosis, and inflammatory responses induced by the activation of NF-κB and NLRP3 inflammasome. Apelin/APJ system also prevents the occurrence of pulmonary edema via activating AKT-NOS3-NO pathway. Moreover, apelin/APJ system accelerates NSCLC cells' proliferation and migration via triggering ERK1/2-cyclin D1 and PAK1-cofilin signaling, respectively. Additionally, apelin/APJ system may act as a predictor in the development of OSAS and PE. Considering the pleiotropic actions of apelin/APJ system, targeting apelin/APJ system may be a potent therapeutic avenue for respiratory diseases.