Gene expression of granulosa and cumulus cells: The prospect inpredicting the quality and developmental competence of oocytesin vitro maturation

In vitro maturation(IVM),a promising assisted reproductive technology(ART),has been evolving in clinical trials and applications.There is a huge potential demand for IVM in clinical practice because it reduces the stimulation of gonadotropins to patients and provides evidence for the safety of neonatal birth.Unfortunately,the maturation rate of oocytes in vitro is not as high as it is in vivo due to a different microenvironment.Moreover,there are still controversies in predicting the developmental capability of oocytes in IVM.The granulosa cells(GCs)and cumulus cells(CCs),closely surrounding the oocytes,play a critical role in oocytes development,while some studies have shown that they can reflect the quality of oocytes.Many studies have been conducted in terms of oocyte quality in transcriptional level in GCs and CCs of mice,Xenopus africanus,and Homo sapiens,which provides important enlightenment for the successful clinical application of IVM.However,no comprehensive reviews about how gene expression profiles affect oocytes quality have been reported.This review aimed to elucidate the gene expression profiles of GCs and CCs that have effects on the quality and developmental competence of oocytes maturation in vitro.And we also put forward a possible idea for ART in the future,integrating all gene expression profiles of GCs and CCs and predicting the quality of the oocytes.

Correction of a CADASIL point mutation using adenine base editors in hiPsCsandbloodvessel organoids

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic small vessel disease caused by mutations in the NOTCH3 gene. However, the pathogenesis of CADASIL remains unclear, and patients have limited treatment options. Here, we use human induced pluripotent stem cells (hiPSCs) generated from the peripheral blood mononuclear cells of a patient with CADASIL carrying a heterozygous NOTCH3 mutation (c.1261C>T, p.R421C) to develop a disease model. The correction efficiency of different adenine base editors (ABEs) is tested using the HEK293T-NOTCH3 reporter cell line. ABEmax is selected based on its higher efficiency and minimization of predicted off-target effects. Vascular smooth muscle cells (VSMCs) differentiated from CADASIL hiPSCs show NOTCH3 deposition and abnormal actin cytoskeleton structure, and the abnormalities are recovered in corrected hiPSC-derived VSMCs. Furthermore, CADASIL blood vessel organoids generated for in vivo modeling show altered expression of genes related to disease phenotypes, including the downregulation of cell adhesion, extracellular matrix organization, and vessel development. The dual adeno-associated virus (AAV) split-ABEmax system is applied to the genome editing of vascular organoids with an average editing efficiency of 8.82%. Collectively, we present potential genetic therapeutic strategies for patients with CADASIL using blood vessel organoids and the dual AAV split-ABEmax system.

Hierarchical Voronoi Structure Inspired by Cat Paw Pads Substantially Enhances Landing Impact Energy Dissipation

When a human lands from a high drop,there is a high risk of serious injury to the lower limbs.On the other hand,cats can withstand jumps and falls from heights without being fatally wounded,largely due to their impact-resistant paw pads.The aim of the present study was to investigate the biomechanism of impact resistance in cat paw pads,propose an optimal hierarchical Voronoi structure inspired by the paw pads,and apply the structure to bionic cushioning shoes to reduce the impact force of landing for humans.The microstructure of cat paw pads was observed via tissue section staining,and a simulation model was reconstructed based on CT to verify and optimize the structural cushioning capacity.The distribution pattern,wall thickness of compartments,thickness ratio of epidermis and dermis,and number of compartments in the model were changed and simulated to achieve an optimal composed structure.A bionic sole was 3D-printed,and its performance was evaluated via compression test and a jumping-landing experiment.The results show that cat paw pads are a spherical cap structure,divided from the outside to the inside into the epidermis,dermis,and compartments,each with different cushioning capacities.A finite element simulation of different cushioning structures was conducted in a cylinder with a diameter of 20 mm and a height of 10 mm,featuring a three-layer structure.The optimal configuration of the three layers should have a uniform distribution with 0.3–0.5 mm wall thickness,a 1:1–2 thickness ratio of epidermis and dermis,and 100–150 compartments.A bionic sole with an optimized structure can reduce the peak impact force and delay the peak arrival time.Its energy absorption rate is about 4 times that of standard sole.When jumping 80,100,and 120 cm,the normalized ground reaction force is also reduced by 8.7%,12.6%and 15.1%compared with standard shoes.This study provides theoretical and technical support for effective protection against human lower limb landing injuries.

Constructing hierarchical ZSM-5 coated with small ZSM-5 crystals via oriented-attachment and in situ assembly for methanol-to-aromatics reaction

Developing hierarchical and nanoscale ZSM-5 catalysts for diffusion-limited reactions has received ever-increasing attention. Here, ZSM-5 architecture integrated with hierarchical pores and nanoscale crystals was successfully prepared via in situ self-assembly of nanoparticles-coated silicalite-1. First, the oriented attachment of amorphous nanoparticles on external surface of silicalite-1 was achieved by controlling the alkalinity of Si-Al coating solution. The partial exposure of the external surface of silicalite-1 ensured the uniform removal of silicon in the bulk phase for the creation of hierarchical pores during the subsequent desilication-recrystallization. The uniform removal of silicon species in the bulk phase was mainly due to the synergistic effect of surface protection and alkaline etching, which could be balanced by regulating the relative amount of tetrapropylammonium cation and OH– in desilication-recrystallization solution. Importantly, the removed silicon from silicalite-1 recrystallized and in situ assembled into final ZSM-5 nanocrystals induced by surface Si-Al nanoparticles. The hierarchical pores and nanoscale crystals on this integrated architecture not only promoted the removal of coke precursors from micropores but also provided large external specific surface (91 m^(2)·g^(-1)) for coke deposition. Consequently, a much longer catalytic lifetime was achieved for methanol-to-aromatics reaction compared to conventional hollow structure ZSM-5 (84 h vs 46 h), with relatively high stability.

How do Cats Resist Landing Injury:Insights into the Multi-level Buffering Mechanism

When humans jump down from a high position,there is a risk of serious injury to the lower limbs.However,cats can jump down from the same heights without any injury because of their excellent ability to attenuate impact forces.The present study aims to investigate the macro/micro biomechanical features of paw pads and limb bones of cats,and the coordination control of joints during landing,providing insights into how cats protect themselves from landing injury.Accordingly,histological analysis,radiological analysis,finite element method,and mechanical testing were performed to investigate the mechanical properties,microstructure,and biomechanical response of the pads and limb bones.In addition,using a motion capture system,the kinematic/kinetic data during landing were analysed based on inverse dynamics.The results show that the pads and limb bones are major contributors to non-impact-injuries,and cats actively couple their joints to adjust the parameters of movement to dissipate the higher impact.Therefore,the paw pads,limb bones,and coordinated joints complement each other and constitute a multi-level buffering mechanism,providing the cat with the sophisticated shock absorption system.This biomechanical analysis can accordingly provide biological inspiration for new approaches to prevent human lower limb injuries.