Mini-organs with big impact:Organoids in liver cancer studies

Hepatocellular carcinoma,the most common primary liver cancer and a leading cause of death,is a difficult disease to treat due to its heterogeneous nature.Traditional models,such as 2D culture and patient-derived xenografts,have not proven effective.However,the development of 3D culture techniques,such as organoids,which can mimic the tumor microenvironment(TME)and preserve heterogeneity and pathophysiological properties of tumor cells,offers new opportunities for treatment and research.Organoids also have the potential for biomarker detection and personalized medication,as well as genome editing using CRISPR/Cas9 to study the behavior of certain genes and therapeutic interventions.This review explores to-the-date development of organoids with a focus on TME modeling in 3D organoid cultures.Further,it discusses gene editing using CRISPR/Cas9 in organoids,the challenges faced,and the prospects in the field of organoids.

Transferrin receptor 1 plays an important role in muscle development and denervation-induced muscular atrophy

Previous studies demonstrate an accumulation of transferrin and transferrin receptor 1(TfR1) in regenerating peripheral nerves.However, the expression and function of transferrin and TfR1 in the denervated skeletal muscle remain poorly understood.In this study, a mouse model of denervation was produced by complete tear of the left brachial plexus nerve.RNA-sequencing revealed that transferrin expression in the denervated skeletal muscle was upregulated, while TfR1 expression was downregulated.We also investigated the function of TfR1 during development and in adult skeletal muscles in mice with inducible deletion or loss of TfR1.The ablation of TfR1 in skeletal muscle in early development caused severe muscular atrophy and early death.In comparison, deletion of TfR1 in adult skeletal muscles did not affect survival or glucose metabolism, but caused skeletal muscle atrophy and motor functional impairment, similar to the muscular atrophy phenotype observed after denervation.These findings suggest that TfR1 plays an important role in muscle development and denervation-induced muscular atrophy.This study was approved by the Institutional Animal Care and Use Committee of Beijing Institute of Basic Medical Sciences, China(approval No.SYXK 2017-C023) on June 1, 2018.

Differences in action potential propagation speed and axon initial segment plasticity between neurons from Sprague-Dawley rats and C57BL/6 mice

Action potentials(APs)in neurons are generated at the axon initial segment(AIS).AP dynamics,including initiation and propagation,are intimately associated with neuronal excitability and neurotransmitter release kinetics.Most learning and memory studies at the single-neuron level have relied on the use of animal models,most notably rodents.Here,we studied AP initiation and propagation in cultured hippocampal neurons from Sprague-Dawley(SD)rats and C57BL/6(C57)mice with genetically encoded voltage indicator(GEVI)-based voltage imaging.Our data showed that APs traveled bidirectionally in neurons from both species;forward-propagating APs(fpAPs)had a different speed than backpropagating APs(bpAPs).Additionally,we observed distinct AP propagation characteristics in AISs emerging from the somatic envelope compared to those originating from dendrites.Compared with rat neurons,mouse neurons exhibited higher bpAP speed and lower fpAP speed,more distally located ankyrin G(AnkG)in AISs,and longer Nav1.2 lengths in AISs.Moreover,during AIS plasticity,AnkG and Nav1.2 showed distal shifts in location and shorter lengths of labeled AISs in rat neurons;in mouse neurons,however,they showed a longer AnkG-labeled length and more distal Nav1.2 location.Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds,different AnkG and Nav1.2 patterns in the AIS,and different AIS plasticity properties,indicating that comparisons between these species must be carefully considered.

Enhanced exciton diffusion from interlayer charge-transfer transitions in PtSe2/MoSe_(2) van der Waals heterojunction

Artificial van der Waals(vdWs)heterostructures offer unprecedented opportunities to explore and reveal novel synergistic electronic and optical phenomena,which are beneficial for the development of novel optoelectronic devices at atomic limits.However,due to the damage caused by the device fabrication process,their inherent properties such as carrier mobility are obscured,which hinders the improvement of device performance and the incorporation of vdWs materials into next-generation integrated circuits.Herein,combining pump-probe spectroscopic and scanning probe microscopic techniques,the intrinsic optoelectronic properties of PtSe_(2)/MoSe_(2)heterojunction were nondestructively and systematically investigated.The heterojunction exhibits a broad-spectrum optical response and maintains ultrafast carrier dynamics(interfacial charge transfer~0.8 ps and carrier lifetime~38.2 ps)simultaneously.The in-plane exciton diffusion coefficient of the heterojunction was extracted(19.4±7.6 cm^(2)∙s^(−1)),and its exciton mobility as high as 756.8 cm^(2)∙V−1∙s^(−1)was deduced,exceeding the value of its components.This enhancement was attributed to the formation of an n-type Schottky junction between PtSe_(2)and MoSe_(2),and its built-in electric field assisted the ultrafast transfer of photogenerated carriers from MoSe_(2)to PtSe_(2),enhancing the in-plane exciton diffusion of the heterojunction.Our results demonstrate that PtSe_(2)/MoSe_(2)is suitable for the development of broadspectrum and sensitive optoelectronic devices.Meanwhile,the results contribute to a fundamental understanding of the performance of various optoelectronic devices based on such PtSe_(2)two-dimensional(2D)heterostructures.

Nucleic acids analysis

Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.

Deafening-induced rapid changes to spine synaptic connectivity in the adult avian vocal basal ganglia

The basal ganglia have been implicated in auditory-dependent vocal learning and plasticity in human and songbirds,but the underlying neural phenotype remains to be clarified.Here,using confocal imaging and three-dimensional electron microscopy,we investigated striatal structural plasticity in response to hearing loss in Area X,the avian vocal basal ganglia,in adult male zebrafinch(Taeniopygia guttata).We observed a rapid elongation of dendritic spines,by approximately 13%,by day 3 after deafening,and a considerable increase in spine synapse density,by approximately 61%,by day 14 after deafening,compared with the controls with an intact cochlea.Thesefind-ings reveal structural sensitivity of Area X to auditory deprivation and suggest that this striatal plasticity might contribute to deafening-induced changes to learned vocal behavior.

Dendritic Morphology Affects the Velocity and Amplitude of Back-propagating Action Potentials

The back-propagating action potential(bpAP)is crucial for neuronal signal integration and synaptic plasticity in dendritic trees.Its properties(velocity and amplitude)can be affected by dendritic morphology.Due to limited spatial resolution,it has been difficult to explore the specific propagation process of bpAPs along dendrites and examine the influence of dendritic morphology,such as the dendrite diameter and branching pattern,using patch-clamp recording.By taking advantage of Optopatch,an all-optical electrophysiological method,we made detailed recordings of the real-time propagation of bpAPs in dendritic trees.We found that the velocity of bpAPs was not uniform in a single dendrite,and the bpAP velocity differed among distinct dendrites of the same neuron.The velocity of a bpAP was positively correlated with the diameter of the dendrite on which it propagated.In addition,when bpAPs passed through a dendritic branch point,their velocity decreased significantly.Similar to velocity,the amplitude of bpAPs was also positively correlated with dendritic diameter,and the attenuation patterns of bpAPs differed among different dendrites.Simulation results from neuron models with different dendritic morphology corresponded well with the experimental results.These findings indicate that the dendritic diameter and branching pattern significantly influence the properties of bpAPs.The diversity among the bpAPs recorded in different neurons was mainly due to differences in dendritic morphology.These results may inspire the construction of neuronal models to predict the propagation of bpAPs in dendrites with enormous variation in morphology,to further illuminate the role of bpAPs in neuronal communication.