Nattokinase as a functional food ingredient:therapeutic applications and mechanisms in age-related diseases

Consumption of natto,a traditional eastern Asian food made of fermented soybeans by Bacillus subtilis,has long been linked to healthy aging and longer human lifespan.As the key thrombolytic ingredient of natto,the serine protease nattokinase(NK)has been developed into a widely-used dietary supplement.NK has shown excellent anti-thrombus,thrombolytic,and anti-inflammation activities that potentially delay aging and provide therapeutic effects on aging-related diseases.In this review,we critically overview the experimental and clinical evidence in the past 20 years that support the beneficial function of NK in the prevention and treatment of aging-related diseases,including cardiovascular diseases,Alzheimer’s disease,other abnormalities and cancer.We focus on the underlying molecular mechanisms and recent advances in application methods that are aimed at further development of NK for healthier aging of modern society.The challenges and unsolved issues in this area are also discussed.

Rotation of Biological Cells:Fundamentals and Applications

Cell rotation is one of the most important techniques for cell manipulation in modern bioscience,as it not only permits cell observation from any arbitrary angle,but also simplifies the procedures for analyzing the mechanical properties of cells,characterizing cell physiology,and performing microsurgery.Numerous approaches have been reported for rotating cells in a wide range of academic and industrial applications.Among them,the most popular are micro-robot-based direct contact manipulation and field-based non-contact methods(e.g.,optical,magnetic,electric,acoustic,and hydrodynamic methods).This review first summarizes the fundamental mechanisms,merits,and demerits of these six main groups of approaches,and then discusses their differences and limitations in detail.We aim to bridge the gap between each method and illustrate the development progress,current advances,and prospects in the field of cell rotation.

Excavating bioactivities of nanozyme to remodel microenvironment for protecting chondrocytes and delaying osteoarthritis

Osteoarthritis(OA)is the main cause of disability in the elderly.Effective intervention in the early and middle stage of osteoarthritis can greatly prevent or slow down the development of the disease,and reduce the probability of joint replacement.However,there is to date no effective intervention for early and middle-stage OA.OA microenvironment mainly destroys the balance of oxidative stress,extracellular matrix synthesis and degradation of chondrocytes under the joint action of biological and mechanical factors.Herein,hollow Prussian blue nanozymes(HPBzymes)were designed via a modified hydrothermal template-free method.The aim of this study was to investigate the effects of HPBzymes on chondrocytes and the progression of OA.The intrinsic bioactivities of HPBzymes were excavated in vitro and in vivo,remodeling microenvironment for significantly protecting chondrocytes and delaying the progression of traumatic OA by inhibiting reactive oxygen species(ROS)and Rac1/nuclear factor kappa-B(NF-κB)signaling in a rat model.HPBzyme significantly diminished interleukin(IL)-1β-stimulated inflammation,extracellular matrix degradation,and apoptosis of human chondrocytes.HPBzyme attenuated the expression of Rac1 and the ROS levels and prevented the release and nuclear translocation of NF-κB.Deeply digging the intrinsic bioactivities of nanozyme with single component to remodel microenvironment is an effective strategy for ROS-associated chronic diseases.This study reveals that excavating the bioactivities of nanomedicine deserves attention for diagnosis and treatment of severe diseases.

Dynamic Landscapes of tRNA Transcriptomes and Translatomes in Diverse Mouse Tissues

Although the function of tRNAs in the translational process is well established,it remains controversial whether tRNA abundance is tightly associated with translational efficiency(TE)in mammals.Moreover,how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed.Here,we measured both tRNA expression using demethylase-tRNA sequencing(DM-tRNA-seq)and TE of mRNAs using ribosome-tagging sequencing(RiboTag-seq)in the brain,heart,and testis of mice.Remarkable variation in the expression of tRNA isodecoders was observed among different tissues.When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons,we observed an expected reduction in the variation of anticodon expression across all samples,an unexpected smaller variation of anticodon usage bias,and an unexpected larger variation of tRNA isotype expression at amino acid level.Regardless of whether or not they share the same anticodons,the isodecoders encoding the same amino acids are co-expressed across different tissues.Based on the expression of tRNAs and the TE of mRNAs,we find that the tRNA adaptation index(tAI)and TE are significantly correlated in the same tissues but not between tissues;and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues.We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms.This study provides a resource for tRNA and translation studies,as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.

International Nuclear Medicine Consensus on the Clinical Use of Amyloid Positron Emission Tomography in Alzheimer’s Disease

Alzheimer’s disease(AD)is the main cause of dementia,with its diagnosis and management remaining challenging.Amyloid positron emission tomography(PET)has become increasingly important in medical practice for patients with AD.To integrate and update previous guidelines in the field,a task group of experts of several disciplines from multiple countries was assembled,and they revised and approved the content related to the application of amyloid PET in the medical settings of cognitively impaired individuals,focusing on clinical scenarios,patient preparation,administered activities,as well as image acquisition,processing,interpretation and reporting.In addition,expert opinions,practices,and protocols of prominent research institutions performing research on amyloid PET of dementia are integrated.With the increasing availability of amyloid PET imaging,a complete and standard pipeline for the entire examination process is essential for clinical practice.This international consensus and practice guideline will help to promote proper clinical use of amyloid PET imaging in patients with AD.

Morphomics via next-generation electron microscopy

The living body is composed of innumerable fine and complex structures.Although these structures have been studied in the past,a vast amount of information pertaining to them still remains unknown.When attempting to observe these ultra-structures,the use of electron microscopy(EM)has become indispensable.However,conventional EM settings are limited to a narrow tissue area,which can bias observations.Recently,new trends in EM research have emerged,enabling coverage of far broader,nano-scale fields of view for two-dimensional wide areas and three-dimensional large volumes.Moreover,cutting-edge bioimage informatics conducted via deep learning has accelerated the quantification of complex morphological bioimages.Taken together,these technological and analytical advances have led to the comprehensive acquisition and quantification of cellular morphology,which now arises as a new omics science termed‘morphomics’.

CAMSAP2 and CAMSAP3 localize at microtubule intersections to regulate the spatial distribution of microtubules

Microtubule networks support many cellular processes and exhibit a highly ordered architecture.However,due to the limited axial resolution of conventional light microscopy,the structural features of these networks cannot be resolved in three-dimensional(3D)space.Here,we used customized ultra-high-resolution interferometric single-molecule localization microscopy to characterize the microtubule networks in Caco2 cells.We found that the calmodulin-regulated spectrin-associated proteins(CAMSAPs)localize at a portion of microtubule intersections.Further investigation showed that depletion of CAMSAP2 and CAMSAP3 leads to the narrowing of the inter-microtubule distance.Mechanistically,CAMSAPs recognize microtubule defects,which often occur near microtubule intersections,and then recruit katanin to remove the damaged microtubules.Therefore,the CAMSAP–katanin complex is a regulatory module for the distance between microtubules.Taken together,our results characterize the architecture of cellular microtubule networks in high resolution and provide molecular insights into how the 3D structure of microtubule networks is controlled.

Structural,Functional,and Molecular Imaging of Autism Spectrum Disorder

Autism spectrum disorder(ASD)is a heterogeneous neurodevelopmental disorder associated with both genetic and environmental risks.Neuroimaging approaches have been widely employed to parse the neurophysiological mechanisms underlying ASD,and provide critical insights into the anatomical,functional,and neurochemical changes.We reviewed recent advances in neuroimaging studies that focused on ASD by using magnetic resonance imaging(MRI),positron emission tomography(PET),or single-positron emission tomography(SPECT).Longitudinal structural MRI has delineated an abnormal developmental trajectory of ASD that is associated with cascading neurobiological processes,and functional MRI has pointed to disrupted functional neural networks.Meanwhile,PET and SPECT imaging have revealed that metabolic and neurotransmitter abnormalities may contribute to shaping the aberrant neural circuits of ASD.Future large-scale,multi-center,multimodal investigations are essential to elucidate the neurophysiological underpinnings of ASD,and facilitate the development of novel diagnostic biomarkers and better-targeted therapy.

Cancer biology deciphered by single-cell transcriptomic sequencing

Tumors are complex ecosystems in which heterogeneous cancer cells interact with their microenvironment composed of diverse immune,endothelial,and stromal cells.Cancer biology had been studied using bulk genomic and gene expression profiling,which however mask the cellular diversity and average the variability among individual molecular programs.Recent advances in single-cell transcriptomic sequencing have enabled a detailed dissection of tumor ecosystems and promoted our understanding of tumorigenesis at single-cell resolution.In the present review,we discuss the main topics of recent cancer studies that have implemented singlecell RNA sequencing(scRNA-seq).To study cancer cells,scRNA-seq has provided novel insights into the cancer stem-cell model,treatment resistance,and cancer metastasis.To study the tumor microenvironment,scRNA-seq has portrayed the diverse cell types and complex cellular states of both immune and non-immune cells interacting with cancer cells,with the promise to discover novel targets for future immunotherapy.