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"Zhu, Chi"
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Ensemble of decision tree reveals potential miRNA-disease associations
In recent years, increasing associations between microRNAs (miRNAs) and human diseases have been identified. Based on accumulating biological data, many computational models for potential miRNA-disease associations inference have been developed, which saves time and expenditure on experimental studies, making great contributions to researching molecular mechanism of human diseases and developing new drugs for disease treatment. In this paper, we proposed a novel computational method named Ensemble of Decision Tree based MiRNA-Disease Association prediction (EDTMDA), which innovatively built a computational framework integrating ensemble learning and dimensionality reduction. For each miRNA-disease pair, the feature vector was extracted by calculating the statistical measures, graph theoretical measures, and matrix factorization results for the miRNA and disease, respectively. Then multiple base learnings were built to yield many decision trees (DTs) based on random selection of negative samples and miRNA/disease features. Particularly, Principal Components Analysis was applied to each base learning to reduce feature dimensionality and hence remove the noise or redundancy. Average strategy was adopted for these DTs to get final association scores between miRNAs and diseases. In model performance evaluation, EDTMDA showed AUC of 0.9309 in global leave-one-out cross validation (LOOCV) and AUC of 0.8524 in local LOOCV. Additionally, AUC of 0.9192+/-0.0009 in 5-fold cross validation proved the model's reliability and stability. Furthermore, three types of case studies for four human diseases were implemented. As a result, 94% (Esophageal Neoplasms), 86% (Kidney Neoplasms), 96% (Breast Neoplasms) and 88% (Carcinoma Hepatocellular) of top 50 predicted miRNAs were confirmed by experimental evidences in literature.
Journal Article
Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells
SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Although population average structure models of the genome were recently reported, there is little experimental data on native structural ensembles, and most structures lack functional characterization. Here we report secondary structure heterogeneity of the entire SARS-CoV-2 genome in two lines of infected cells at single nucleotide resolution. Our results reveal alternative RNA conformations across the genome and at the critical frameshifting stimulation element (FSE) that are drastically different from prevailing population average models. Importantly, we find that this structural ensemble promotes frameshifting rates much higher than the canonical minimal FSE and similar to ribosome profiling studies. Our results highlight the value of studying RNA in its full length and cellular context. The genomic structures detailed here lay groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics.
Lan et al. report RNA structure ensembles across the entire SARSCoV-2 genome in infected human cells at single nucleotide resolution. They find alternative RNA conformations critical for promoting near-native frameshifting rates in ORF1ab.
Journal Article
Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer’s disease
Amyloid-beta (Aβ) plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD). The physiological capacity of peripheral tissues and organs in clearing brain-derived Aβ and its therapeutic potential for AD remains largely unknown. Here, we measured blood Aβ levels in different locations of the circulation in humans and mice, and used a parabiosis model to investigate the effect of peripheral Aβ catabolism on AD pathogenesis. We found that blood Aβ levels in the inferior/posterior vena cava were lower than that in the superior vena cava in both humans and mice. In addition, injected
125
I labeled Aβ40 was located mostly in the liver, kidney, gastrointestinal tract, and skin but very little in the brain; suggesting that Aβ derived from the brain can be cleared in the periphery. Parabiosis before and after Aβ deposition in the brain significantly reduced brain Aβ burden without alterations in the expression of amyloid precursor protein, Aβ generating and degrading enzymes, Aβ transport receptors, and AD-type pathologies including hyperphosphorylated tau, neuroinflammation, as well as neuronal degeneration and loss in the brains of parabiotic AD mice. Our study revealed that the peripheral system is potent in clearing brain Aβ and preventing AD pathogenesis. The present work suggests that peripheral Aβ clearance is a valid therapeutic approach for AD, and implies that deficits in the Aβ clearance in the periphery might also contribute to AD pathogenesis.
Journal Article
An upper-limb teleoperation exoskeleton with stepless arm-length parameterization and adaptive force-triggered impedance blending
Remote control technology is a core means of ensuring personnel safety in high-risk scenarios such as deep-sea exploration and nuclear facility maintenance. However, existing exoskeleton teleoperations suffer from drawbacks such as discretized arm length adjustment, insufficient dynamic control adaptability, and limited execution accuracy. This study proposes a reproducible unilateral upper limb exoskeleton teleoperation system, employing a 7-DOF active drive architecture (3 DOF for the shoulder, 1 DOF for the elbow, and 3 DOF for the wrist) to match the kinematic characteristics of the human upper limb. The system integrates four key designs: low-inertia, high-reaction joints (weight reduction using carbon fiber and aluminum alloy), an ergonomic alignment mechanism adapted to upper arm circumferences of 74.8–105.7 mm, a 6-DOF passive compensation module for scapulothoracic wall motion, and a digital adaptive arm length adjustment mechanism (achieving stepless adjustment and dynamic updating of the URDF model through a sliding rheostat). The control strategy adopts a hybrid scheme of “master-end position impedance control and slave-end force-based impedance feedback,” modeled based on the Lagrange equation, introducing adaptive weighted coefficient balance trajectory tracking and force feedback compliance, and verifying global asymptotic stability using Lyapunov functions and the LaSalle invariance principle. The experiment used the Franka Panda robot as a platform, based on a Linux real-time kernel and ROS architecture, with joint position data transmitted via 500 Hz Ethernet. Master-slave teleoperation achieved a mirrored reproduction of a spatial figure-eight trajectory, and gravity compensation effectively offset the load. Ablation experiments showed that the peak contact force in group C3 decreased to 7.41 N (a 68.8% reduction from baseline); the sum of squared residuals in arm length measurement was
, and the deviation after multiple wearing cycles was
mm. The experiment confirmed that the system overcomes the adaptability and robustness deficiencies of traditional systems, achieving high-precision master-slave synchronization and load compensation. It meets the teleoperation needs of high-risk scenarios and can also provide a rehabilitation training platform for hemiplegic patients, demonstrating broad application prospects.
Journal Article
Beyond the stomach: the association between Helicobacter pylori and the spectrum of digestive cancers
Helicobacter pylori ( H. pylori ) is a Group 1 gastric carcinogen increasingly implicated in extragastric digestive malignancies. This review synthesizes evidence on its role in liver, biliary, esophageal, colorectal, and pancreatic cancers. Based on its unique spiral morphology, flagellar motility bundle, and urease activity-mediated acidic niche adaptation, H. pylori disrupts host cellular homeostasis through multifactorial virulence mechanisms involving CagA/VacA synergy, and exploits antigenic variation and immunomodulatory strategies to achieve persistent gastric mucosal colonization and chronic infection. Emerging evidence suggests associations between H. pylori infection and nongastric digestive cancers, though relationships vary by site. For hepatocellular carcinoma (HCC), epidemiological studies indicate increased risk (OR 4.75), particularly with HCV coinfection, but mechanistic and cohort data remain conflicting. Biliary tract cancer (BTC) shows stronger epidemiological links, especially for cholangiocarcinoma (OR 4.18), supported by virulence factor detection. In esophageal cancer, H. pylori particularly CagA+ strains demonstrates a protective effect against adenocarcinoma but no significant association with squamous cell carcinoma. Colorectal cancer exhibits complex associations, with meta-analyses suggesting increased risk in East Asian populations and potential benefits from eradication therapy. Pancreatic cancer links remain inconsistent. Proposed mechanisms of H. pylori in extragastric cancers include chronic inflammation, virulence factor activity and microbiome disruption. This comprehensive review synthesizes contemporary evidence on the bacterium’s role in non-gastric digestive malignancies, examines pathways underlying its oncogenicity, and outlines translational implications for risk stratification and therapeutic innovation.
Journal Article
Tempo-spatial variations of zooplankton communities in relation to environmental factors and the ecological implications: A case study in the hinterland of the Three Gorges Reservoir area, China
To expand the knowledge on the tempo-spatial patterns of zooplankton and the key modulated factors in urban aquatic ecosystem, we investigated zooplankton and water quality from April 2018 to January 2019 in the hinterland of the Three Gorges Reservoir area, Wanzhou City of China. The results indicated that water quality indicated by the trophic state index (TSI) reached a state of mesotrophication to light eutrophication in the Yangtze River, and a state of moderate- to hyper- eutrophication in its tributaries. Based on the biomass of zooplanktons, Asplanchna priodonta was the most common specie in April; Encentrum sp., Filinia cornuta and Epiphanes senta were the most noticeable species in summer; Cyclopoida Copepodid, Sinocalanus dorrii and Philodina erythrophthalma became the dominant species in winter. Generally, rotifers prevailed in April and August, and copepods became the most popular in January. According to canonical correspondence analysis, nitrate, temperature (T), ammonia, water level and permanganate index (COD Mn ) significantly influenced the community structure of zooplankton ( p < 0.05). The dominant species shifts of zooplankton were partly associated with nutrient level (nitrate and ammonia) under periodic water level fluctuations. Rotifers and protozoans were characterized as high T adapted and COD Mn -tolerant species comparing with cladocerans and copepods. The ratio of microzooplankton to mesozooplankton (P micro/meso ) has presented a strongly positive relationship with T ( p < 0.001), as well as P micro/meso and COD Mn ( p < 0.001). It implied that zooplankton tended to miniaturize individual size via species shift under high T and/or COD Mn conditions induced by global warming and human activities. The information hints us that climate change and human activities are likely to produce fundamental changes in urban aquatic ecosystem by reorganizing biomass structure of the food web in future.
Journal Article
Clinical Research on Alzheimer’s Disease: Progress and Perspectives
Alzheimer’s disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
Journal Article
Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis
Isocitrate dehydrogenase 1 and 2 ( IDH1/2 ) mutations and their key effector 2-hydroxyglutarate (2-HG) have been reported to promote oncogenesis in various human cancers. To elucidate molecular mechanism(s) associated with IDH1/2 mutations, we established mouse embryonic fibroblasts (MEF) cells and human colorectal cancer cells stably expressing cancer-associated IDH1 R132C or IDH2 R172S , and analyzed the change in metabolic characteristics of the these cells. We found that IDH1/2 mutants induced intracellular 2-HG accumulation and inhibited cell proliferation. Expression profile analysis by RNA-seq unveiled that glucose transporter 1 (Glut1) was induced by the IDH1/2 mutants or treatment with 2-HG in the MEF cells. Consistently, glucose uptake and lactate production were increased by the mutants, suggesting the deregulation of glucose metabolism. Furthermore, PI3K/Akt/mTOR pathway and Hif1α expression were involved in the up-regulation of Glut1. Together, these results suggest that Glut1 is a potential target regulated by cancer-associated IDH1/2 mutations.
Journal Article