A self-supervised spatio-temporal attention network for video-based 3D infant pose estimation.

General movement and pose assessment of infants is crucial for the early detection of cerebral palsy (CP). Nevertheless, most human pose estimation methods, in 2D or 3D, focus on adults due to the lack of large datasets and pose annotations on infants. To solve these problems, here we present a model known as YOLO-infantPose, which has been fine-tuned, for infant pose estimation in 2D. We further propose a self-supervised model called STAPose3D for 3D infant pose estimation based on videos. We employ multi-view video data during the training process as a strategy to address the challenge posed by the absence of 3D pose annotations. STAPose3D combines temporal convolution, temporal attention, and graph attention to jointly learn spatio-temporal features of infant pose. Our methods are summarized into two stages: applying YOLO-infantPose on input videos, followed by lifting these 2D poses along with respective confidences for every joint to 3D. The employment of the best-performing 2D detector in the first stage significantly improves the precision of 3D pose estimation. We reveal that fine-tuned YOLO-infantPose outperforms other models tested on our clinical dataset as well as two public datasets MINI-RGBD and YouTube-Infant dataset. Results from our infant movement video dataset demonstrate that STAPose3D effectively comprehends the spatio-temporal features among different views and significantly improves the performance of 3D infant pose estimation in videos. Finally, we explore the clinical application of our method for general movement assessment (GMA) in a clinical dataset annotated as normal writhing movements or abnormal monotonic movements according to the GMA standards. We show that the 3D pose estimation results produced by our STAPose3D model significantly boost the GMA prediction performance than 2D pose estimation. Our code is available at github.com/wwYinYin/STAPose3D.

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.

MCU complex: Exploring emerging targets and mechanisms of mitochondrial physiology and pathology.

BACKGROUND: Globally, the onset and progression of multiple human diseases are associated with mitochondrial dysfunction and dysregulation of Ca2+ uptake dynamics mediated by the mitochondrial calcium uniporter (MCU) complex, which plays a key role in mitochondrial dysfunction. Despite relevant studies, the underlying pathophysiological mechanisms have not yet been fully elucidated. AIM OF REVIEW: This article provides an in-depth analysis of the current research status of the MCU complex, focusing on its molecular composition, regulatory mechanisms, and association with diseases. In addition, we conducted an in-depth analysis of the regulatory effects of agonists, inhibitors, and traditional Chinese medicine (TCM) monomers on the MCU complex and their application prospects in disease treatment. From the perspective of medicinal chemistry, we conducted an in-depth analysis of the structure-activity relationship between these small molecules and MCU and deduced potential pharmacophores and binding pockets. Simultaneously, key structural domains of the MCU complex in Homo sapiens were identified. We also studied the functional expression of the MCU complex in Drosophila, Zebrafish, and Caenorhabditis elegans. These analyses provide a basis for exploring potential treatment strategies targeting the MCU complex and provide strong support for the development of future precision medicine and treatments. KEY SCIENTIFIC CONCEPTS OF REVIEW: The MCU complex exhibits varying behavior across different tissues and plays various roles in metabolic functions. It consists of six MCU subunits, an essential MCU regulator (EMRE), and solute carrier 25A23 (SLC25A23). They regulate processes, such as mitochondrial Ca2+ (mCa2+) uptake, mitochondrial adenosine triphosphate (ATP) production, calcium dynamics, oxidative stress (OS), and cell death. Regulation makes it a potential target for treating diseases, especially cardiovascular diseases, neurodegenerative diseases, inflammatory diseases, metabolic diseases, and tumors.

AgAu-modified quasi-MIL-53 hybrid nanozymes with triple enzyme-like activities for boosting biocatalytic disinfection.

Metal-organic frameworks (MOFs) have great potential for combating pathogenic bacterial infections and are expected to become an alternative to antibiotics. However, organic linkers obstruct and saturate the inorganic nodes of MOF structures, making it challenging to utilize the applied potential of metal centers. Here, we combined controlled ligand decarboxylation with noble metal nanoparticles to rationally remodel MIL-53, resulting in a hybrid nanozyme (AgAu@QMIL-53, AAQM) with excellent multiple enzyme-like activities that both eradicate bacteria and promote diabetic wound healing. Specifically, benefitting from oxidase (OXD)-like and peroxidase (POD)-like activities, AAQM converts oxygen (O2) and hydrogen peroxide (H2O2) into superoxide anion radicals (O2-) and hydroxyl radicals (OH) to eradicate bacteria. In in vitro antibacterial experiments, AAQM exhibited favorable killing efficacy against Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) (>99 %). Notably, due to its superoxide (SOD)-like activity and outstanding reactive nitrogen species (RNS) elimination capacity, AAQM can produce adequate O2 and alleviate oxidative stress in diabetic wounds. Benefiting from the rational modification of MIL-53, the synthesized hybrid nanozyme can effectively kill bacteria while alleviating oxidative stress and ultimately promote infected diabetic wound healing. Overall, this biomimetic enzyme-catalyzed strategy will bring enlightenment to the design of self-antibacterial agents for efficient disinfection and wound healing simultaneously.

Functions and targets of miRNAs in pharmacological and toxicological effects of major components of Tripterygium wilfordii Hook F.

Tripterygium wilfordii Hook F (TwHF) has a long history of use as a traditional Chinese medicine and has been widely administered to treat various inflammatory and autoimmune diseases. MicroRNAs (miRNAs) are endogenous, short, non-coding RNAs that regulate gene expression post-transcriptionally. They participate in the efficacies and even toxicities of the components of TwHF, rendering miRNAs an appealing therapeutic strategy. This review summarizes the recent literature related to the roles and mechanisms of miRNAs in the pharmacological and toxicological effects of main components of TwHF, focusing on two active compounds, triptolide (TP) and celastrol (CEL). Additionally, the prospects for the "You Gu Wu Yun" theory regarding TwHF nephrotoxicity are presented.

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 SAN (Spatial Autocorrelation Normalization) 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.

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.

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.

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 ).

Association between metabolic syndrome components and impulse control disorders in Parkinson's disease.

Background: Current evidence on management of impulse control disorders (ICDs) in Parkinson's disease (PD) remains scarce, and exploring modifiable risk factors is crucial. Objective: We evaluated the profiles of ICDs in PD patients and aimed to determine the associations between ICDs, metabolic syndrome components and other clinical features. Methods: We enrolled patients diagnosed with PD in this study and conducted comprehensive clinical assessments. Results: We recruited 39 PD patients with ICDs and 66 PD patients without ICDs. Out of the 39 patients with ICDs, 19 (48.7%) had one impulse control disorder, while 20 (51.3%) had two or more. The most commonly reported symptom of ICDs was compulsive eating (48.7%). Significant differences were observed between the PD patients with and without ICDs in terms of their HbA1c levels, history of diabetes mellitus, dopamine agonist use, levodopa equivalent dose of dopamine agonists (LED DA), and Hamilton Depression Rating Scale (HAMD) scores. HbA1c levels were significantly higher in the PD patients with compulsive eating. Stepwise logistic regression analyses were performed with the dependent variables of ICDs (yes/no) and compulsive eating (yes/no). Among the 105 PD patients, those with ICDs exhibited higher levels of HbA1c, HAMD score and LED DA than those without ICDs (p < 0.01). Among 39 PD patients with ICDs, those with compulsive eating exhibited higher levels of HbA1c (OR = 2.148, 95% CI = 1.004-4.594, p < 0.05). Among 105 PD patients, those with compulsive eating exhibited higher levels of HbA1c, LED DA and HAMD score (p < 0.05). Conclusion: This study provides insights into the profiles of ICDs in PD patients and their associations with various clinical features. Compulsive eating was the most common ICDs symptom reported. Notably, HbA1c levels were found to be higher in patients with compulsive eating, indicating that poor blood glucose control may be a potential risk factor for ICDs in PD. However, it should be noted that the higher HbA1c levels could also be a consequence of compulsive eating rather than a causal factor for ICDs in PD. Further research is needed to confirm the modifiable risk factors for ICDs in PD.

Development of a Golgi-targeted superoxide anion fluorescent probe for elucidating protein GOLPH3 function in myocardial ischemia-reperfusion injury.

Superoxide anion (O2•-) is an important reactive oxygen species (ROS) and participates in various physiological and pathological processes in the organism. The O2•- burst induced by ischemia-reperfusion (I/R) is associated with cardiovascular disease and promotes the cell apoptosis. In this work, a turn-on type Golgi-targeting fluorescent probe Gol-Cou-O2•- was rationally designed for sensitive and selective detection of O2•-. The minimum detection limit concentration for O2•- was about 3.9 × 10-7 M in aqueous solution. Gol-Cou-O2•- showed excellent capacity of detecting exogenous and endogenous O2•- in living cells and zebrafish, and was also used to capture the up-regulated O2•- level during the duration of I/R process in cardiomyocytes. Golgi Phosphoprotein 3 (GOLPH3) is a potential Golgi stress marker protein and plays a key role in cells apoptosis during I/R. The fluorescence imaging and flow cytometry assay results indicated that silencing GOLPH3 through siRNA could give rise to the down-regulated O2•- level and alleviation of apoptosis in I/R myocardial cells. Thus, development of Gol-Cou-O2•- provides a diagnostic tool for myocardial oxidative stress injury and distinct insights on roles of GOLPH3 in myocardial I/R injury.

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.

Development of a Golgi-targeted fluorescent chemosensor for detecting ferrous ions overload under Golgi stress.

Ferrous ion (Fe2+) is a crucial metal ion in the body and participates in the diseases related to oxidation and reduction. Golgi apparatus is the main subcellular organelle of Fe2+ transport in cells, and the stability of its structure is related to the Fe2+ at an appropriate concentration. In this work, a turn-on type Golgi-targeting fluorescent chemosensor Gol-Cou-Fe2+ was rationally designed for sensitive and selective detection of Fe2+. Gol-Cou-Fe2+ showed excellent capacity of detecting exogenous and endogenous Fe2+ in HUVEC and HepG2 cells. It was used to capture the up-regulated Fe2+ level during the hypoxia. Moreover, the fluorescence of sensor was enhanced over time under Golgi stress combining with the reduce of Golgi matrix protein GM130. However, elimination of Fe2+ or addition of nitric oxide (NO) would restore the fluorescence intensity of Gol-Cou-Fe2+ and the expression of GM130 in HUVEC. Thus, development of chemosensor Gol-Cou-Fe2+ provides a new window for tracking Golgi Fe2+ and elucidating Golgi stress-related diseases.

Glycometabolism reprogramming: Implications for cardiovascular diseases.

Glycometabolism is well known for its roles as the main source of energy, which mainly includes three metabolic pathways: oxidative phosphorylation, glycolysis and pentose phosphate pathway. The orderly progress of glycometabolism is the basis for the maintenance of cardiovascular function. However, upon exposure to harmful stimuli, the intracellular glycometabolism changes or tends to shift toward another glycometabolism pathway more suitable for its own development and adaptation. This shift away from the normal glycometabolism is also known as glycometabolism reprogramming, which is commonly related to the occurrence and aggravation of cardiovascular diseases. In this review, we elucidate the physiological role of glycometabolism in the cardiovascular system and summarize the mechanisms by which glycometabolism drives cardiovascular diseases, including diabetes, cardiac hypertrophy, heart failure, atherosclerosis, and pulmonary hypertension. Collectively, directing GMR back to normal glycometabolism might provide a therapeutic strategy for the prevention and treatment of related cardiovascular 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.

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.