Mitochondria are an important target of photobiomodulation in cardiomyocytes

Photobiomodulation(PBM)has been shown to delay the pathological process of heart failure,but the exact mechanism of action is not clear.Mitochondria occupy one-third of the volume of mammalian cardiomyocytes(CMs)and are central transport stations for CM energy metabolism.Therefore,in this study,we explored the regulatory effects of 630 nm light-emitting diodes(LED-Red)on the mitochondria of CMs.The results show that LED-Red-based PBM promotes adenosine triphosphate(ATP)synthesis by upregulating the expression of glycolipid metabolizing enzymes.Correspondingly,there was an improvement in the activity of succinate dehydrogenase(SDH),a key enzyme in the mitochondrial electron transport chain,and the mitochondrial membrane potential.Meanwhile,LED-Red affected the state of mitochondrial oxidative stress and promoted the generation of reactive oxygen species(ROS),but the increased ROS production did not damage the CMs.In addition,mitochondrial division and fusion were also affected by the stimulation of LED-Red.Finally,PBM treatment led to a significant increase in transcript levels of mitochondrial transcription factor A(TFAM),which controls the stability of the mitochondrial genome.Collectively,irradiation with LEDs at 630 nm played a regulatory role in mitochondrial function,suggesting that mitochondria appear to be the recipients of PBM treatment.This study provides more insights into the mechanisms underlying PBM treatment in heart diseases.

LncRNA ZFAS1 regulates cardiomyocyte differentiation of human embryonic stem cells

Background:Cardiomyocytes derived from human embryonic stem cells(hESCs)are regulated by complex and stringent gene networks during differentiation.Long non-coding RNAs(lncRNAs)exert critical epigenetic regulatory functions in multiple differentiation processes.However,the involvement of lncRNAs in the differentiation of hESCs into cardiomyocytes has not yet been fully elucidated.Here,we identified the key roles of ZFAS1(lncRNA zinc finger antisense 1)in the differentiation of cardiomyocytes from hESCs.Methods:A model of cardiomyocyte differentiation from stem cells was established using the monolayer differentiation method,and the number of beating hESCs-derived cardiomyocytes was calculated.Gene expression was analyzed by quantitative real-time PCR(qRTPCR).Immunofluorescence assays were performed to assess the expression of cardiac troponin T(cTnT)andα-actinin protein in cardiomyocytes.Results:qRT-PCR showed that ZFAS1 expression in the mesoderm was significantly higher than that in embryonic stem cells,cardiac progenitor cells,and cardiomyocytes.Knockdown of ZFAS1 inhibited cardiomyocyte differentiation from hESCs,which was characterized by reduced expression of the cardiac-specific markers cTnT,α-actinin,myosin heavy chain 6(MYH6),and myosin heavy chain 7(MYH7).In contrast,ZFAS1 overexpression remarkably increased the percentage of spontaneously beating cardiomyocytes.In terms of the mechanism,we found that ZFAS1 is an antisense lncRNA at the 5′end of the protein-coding gene ZNFX1.Knockdown of ZFAS1 could increase the mRNA expression level of ZNFX1.Furthermore,qRT-PCR demonstrated that the silencing of ZNFX1 led to an increase in cardiac-specific markers that predicted the promotion of cardiomyocyte differentiation.Conclusion:Altogether,these data suggest that lncRNA-ZFAS1 is required for cardiac differentiation by functionally inhibiting the expression of ZNFX1,which may provide a reference for the treatment of heart disease to a certain extent.

生物合成高能化学物质

从分子到细胞,从个体到社会,能量的需求和转化无处不在。探索高能物质的合成与利用,具有较重要的科学意义和应用价值。目前高能物质的化学合成通常污染较大、耗能较高,且往往副产物较多,难以分离纯化。相较于传统的化学合成方法,生物合成具有绿色环保和高效利用清洁能源等特点,是符合国家“碳中和”目标的新型合成路径。高能物质的生物合成,将是未来的迅速发展方向之一。本文将从能源物质、含能材料和天然高能物质三个方面,选取四种代表性高能物质,介绍其生物合成途径及与之相关的关键金属酶。

Altered expression profile of long non-coding RNAs during heart aging in mice

Objective:Long noncoding RNAs(lncRNAs)play an important role in regulating the occurrence and development of cardiovascular diseases.However,the role of lncRNAs in heart aging remains poorly understood.The objective of this study was to identify differentially expressed lncRNAs in the heart of aging mice and elucidate the relevant regulatory pathways of cardiac aging.Materials and methods:Echocardiography was used to detect the cardiac function of 18-months(aged)and 3-months(young)old C57BL/6 mice.Microarray analysis was performed to unravel the expression profiles of lncRNAs and mRNAs,and qRT-PCR to verify the highly dysregulated lncRNAs.Results:Our results demonstrated that the heart function in aged mice was impaired relative to young ones.Microarray results showed that 155 lncRNAs were upregulated and 37 were downregulated,and 170 mRNAs were significantly upregulated and 44 were remarkably downregulated in aging hearts.Gene ontology analysis indicated that differentially expressed genes are mainly related to immune function,cell proliferation,copper ion response,and cellular cation homeostasis.KEGG pathway analysis showed that the differentially expressed mRNAs are related to cytokine-cytokine receptor interaction,inflammatory mediator regulation of TRP channels,and the NF-kappa B signaling pathway.Conclusion:These results imply that the differentially expressed lncRNAs may regulate the development of heart aging.This study provides a new perspective on the potential effects and mechanisms of lncRNAs in heart aging.

Discussion and Research on Orthopedic Biomechanics Testing Technology

With the continuous development of today's science and technology,orthopedic research has also achieved continuous updates in materials and machinery.In this case,the mechanics testing technology of orthopedics also needs to be further updated and developed,so that it can effectively meet the requirement for today's orthopedic mechanical testing.Based on this,this article analyzes several advanced orthopedic mechanics testing techniques.It is hoped that this analysis can provide a reference for the good application and development of orthopedic mechanics testing technology.

A Rhein-Based Rh(Ⅲ) Arene Complex with Anti-tumor Cell Proliferative Activity Inhibits RNA Demethylase FTO

Metallodrugs with fine-tuned coordination between metals and bioactive ligands can achieve cytotoxic effects in cancer therapy and have been considered as a new approach for drug design.However,it has yet to be elucidated whether these metallodrugs target epitranscriptomic proteins for gene expression regulation.This report describes a rhein-based Rh(l)-arene complex,Rh1,that exhibited promising antiproliferative ffects in several tumor cellines.Rh1 induced cell death through the autophagy,cell cycle arrest,and accumulation of intracllular reactive oxygen species(ROs),In addition,Rh1 upregulated the global N^(6)-methyladenosine(m^(6)A)levels in A549 cells in the fat mass-and obesity-associated protein(FTO)-dependent manner.Collectively,the metal-based FTO inhibitor Rh1 effectively suppressed tumor cell proliferation and modulated the abundance of cellular m^(6)A,highlighting the potential of metal-based agents to target and regulate epitranscriptomics for tumor suppression.

Ferroptosis-inducing inorganic arsenic(II)sulfide nanocrystals enhance immune activation

Arsenic(II)sulfide is a stable inorganic arsenic compound with a different valence from arsenic trioxide,and has been widely applied to treat various diseases with low toxic side effects for a long time.However,its low solubility and complicated formulations restrict its further applications in modern medical industry.Meanwhile,as the tumour with the highest incidence rate among women,the low recurrence risk of breast cancer has been confirmed to be closely related to the high infiltration of immune cells.Herein,we synthesized and filtered novel biocompatible PEGylated arsenic(II)sulfide nanocrystals AsS@PEG with a size of 93.14±0.49 nm by the gel method,which displayed excellent anticancer and immune activation activity in breast cancer model.Proteomic analysis suggested that the AsS@PEG induce ferroptosis in cancer cells and further activate antitumour immune responses via B-cell lymphoma 9-like(BCL9L)protein inhibition.Furthermore,mechanism studies revealed notable glutathione peroxidase 4(GPX4)downregulation in cancer cells,dendritic cells(DCs)maturation and subsequent effector CD8^(+)T-cells production induced by the AsS@PEG in the tumour microenvironment.This study highlights biocompatible arsenic(II)sulfide nanocrystals that induce ferroptotic cell death and activate antitumour immune responses,providing insights into the path towards the immunotherapy assisted chemotherapy for breast cancer.

Actuation performances of catkin fibers reinforced thiol-acrylate main-chain liquid crystalline elastomer

Liquid crystalline elastomers(LCEs)have been utilized as an important class of smart actuator materials.However,the modest actuation mechanical and robustness performances remain a challenge.Inspired by the specific structures,well mechanical properties and physico-chemical characteristics of some natural plant fibers,a composite of thiol-acrylate main-chain LCE matrix incorporated with catkin fibers is designed and developed.The catkin fibers build a network as reinforcement phase,and demon-strate effective compatibility and integration property with the matrix,their high flexibility can be adapted to the large deforma-tional performance of LCE matrix.The prepared LCE composite demonstrates strong mechanical actuation properties.The mod-ulus and driving force triggered by the stimuli are obviously increased.The tensile strength and fatigue failure resistant prop-erty under high loadings and repeated cycles of thermal actua-tion or photothermal actuation are greatly enhanced.While the stimulus response deformation rate,phase transition temperature and liquid crystal phase structure of the LCE matrix,and so on,do not weaken or change.This work promotes the LCE materi-als’application potential and broadens the application value of natural plant fibers.

Cyclin L1 controls cardiomyocyte proliferation and heart repair after injury

Dear Editor,Myocardial infarction(MI)is characterized by the loss of functional cardiomyocyte(CM)in the heart,resulting in cardiac systolic dysfunction and heart failure.1,2 Increasing evidence suggested that in the heart of neonatal mice after apical resection(AR),the CM can proliferate and regenerate myocardium to repair the heart.While in the heart of adult mice after MI,the CM loses the ability to re-enter the cell cycle but undergoes hypertrophic growth.

Electromagnetic field-enhanced chiral dimanganese trioxide nanoparticles mitigate Parkinson’s disease

The misfolding and aggregation ofα-synuclein(α-syn)is closely associated with Parkinson’s disease(PD).Here,chiral dimanganese trioxide(Mn_(2)O_(3))nanoparticles(NPs)were prepared for PD treatment enhanced by a noninvasive electromagnetic field(MF).The affinity constants of D-NPs towardα-syn monomer(mono)orα-syn fibril were 3.5 times or 5.2 times higher,respectively,than those of L-NPs,and the mechanical force generated by NPs under a MF further promoted the interaction between NPs andα-syn to amplify the difference between L-NPs and D-NPs.As the synergy effect of the preferentially affinity ability and MF-induced mechanical forces,D-NPs exhibited a better inhibitory efficiency onα-syn fibrillization than L-NPs.Furthermore,after differentially cellular uptake of L-/D-NPs via the caveolin-mediated pathway,as reactive oxygen species(ROS)-scavengers,D-NPs possess higher efficiency in decreasing intracellular ROS level than L-NPs to provide higher cytoprotective efficiency to neuron cells.In vivo data showed that after treatment with D-NPs under a MF for 60 days,α-syn concentration in the cerebrospinal fluid of PD mice decreased 81%,while dopamine level in the brain of PD mice increased 2.3-fold.These findings indicated the potential of utilizing the synergic interplay of chiral NPs and MF for treating disease and opened a new path to explore the nanoscale chirality for regulating the biological effect.

Recent progress of traditional Chinese medical science based on theory of biophoton

With the development of biophotonics, bio- photon detection technology has been appropriately used. In this paper, the main features and fundamental concep- tions of biophotonics were introduced basically. Then the coherence theory of biophoton emission was reviewed. Furthermore, based on this coherence concept, the quantum theory of traditional Chinese medicine （TCM） and properties of Chinese medicinal herbs were presented. To show the nature of biophoton emission in living systems and clarify its basic detection mechanism, high sensitive detection system which allows non-invasive and non-destructive （or less） recording was finally presented.

A ferroptosis-inducing iridium(III) complex

Ferroptosis is a recently emerging non-apoptotic mode of cell death involving the production of iron-dependent reactive oxygen species(ROS).Here we described a mitochondria-targeted iridium(III)complex Ir FN that exhibited potent antiproliferative activity against a variety of cancer cells,especially the A2780 human ovarian cancer cells,through the ferroptosis pathways.Mechanistic studies by label-free quantitative proteomics profiling indicated that heme oxygenase 1(HMOX1)-mediated ferroptosis process was activated by Ir FN.The study on iron-dependent cell death,ROS accumulation,lipid peroxidation,and over released iron further confirmed the ferroptosis processes.m RNA transcription quantification,in vitro over-expression of HMOX1,and RNAi-mediated knock-down experiments suggested that Ir FN activated the over-expression of HMOX1.Our report revealed the first case of anticancer iridium complex leading to ferroptosis,highlighting ferroptosis as a promising approach in future design of metallodrugs.

Kinetic Investigation of a Cucurbit[7]uril-Based Pseudo[6]rotaxane System by Microfluidic Nuclear Magnetic Resonance

It is challenging to investigate fast supramolecular processes due to the lack of appropriate characterization methods with high structural resolution.In this study,microfluidic nuclear magnetic resonance(μFNMR)spectroscopy was employed to monitor the kinetics of threading and dethreading of a pseudo[6]rotaxane system.By employing high time resolutionμF-NMR,1 H and two-dimensional(2D)rotating frame nuclear Overhauser effect spectroscopy(ROESY)NMR spectra were recorded at any time point within 1.5 s after the onset of the process.This technique enabled the successful identification of kinetic intermediates and rate-determining steps,usually impossible to determine by other spectroscopic techniques.Thus,our study demonstrates the capability ofμF-NMR in investigating the mechanism of complex supramolecular systems.

Regulation of graphdiyne-based nanozymes with enhanced oxidaselike activity by cobalt and nitrogen codoping

The development of nanozymes with excellent intrinsic oxidase-like activity and specificity has received increasing interest.Graphdiyne(GDY)could be a promising choice for designing nanozymes with enhanced oxidase(OXD)-like activity due to its unique structure and properties.Herein,Co-N-GDY with high OXD activity but no peroxidase(POD)activity was synthesized by codoping of cobalt(Co)and nitrogen(N)into GDY and compared with other GDY-based nanozymes(including GDY,Co-GDY,and N-GDY).Upon analyzing the doping effect of Co and N on the OXD-like and POD-like activities,we found that the combination of Co and N in GDY played a significant role in enhancing the OXD-like activity,and even reversed the POD-like activity of N-GDY to OXD-like activity of Co-N-GDY.The electrochemical experiment and the theoretical calculations provided an explanation for the mechanism and showed that the activity was closely linked to the reduction ability of O_(2) or H_(2)O_(2) on the nanozyme substrates,which was determined by the ratedetermining step of the catalytic reaction.