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Abstract A healthy heart comprises various cell types, including cardiomyocytes, endothelial cells, fibroblasts, immune cells, and among others, which work together to maintain optimal cardiac function. These cells engage in complex communication networks, known as cell-cell interactions (CCIs), which are essential for homeostasis, cardiac structure, and efficient function. However, in the context of cardiac diseases, the heart undergoes damage, leading to alterations in the cellular composition. Such pathological conditions trigger significant changes in CCIs, causing cell rearrangement and the transition between cell types. Studying these interactions can provide valuable insights into cardiac biology and disease mechanisms, enabling the development of new therapeutic strategies. While the development of cardiac organoids and advanced 3D co-culture technologies has revolutionized in vitro studies of CCIs, recent advancements in single-cell and spatial multi-omics technologies provide researchers with powerful and convenient tools to investigate CCIs at unprecedented resolution. This article provides a concise overview of CCIs observed in both normal and injured heart, with an emphasis on the cutting-edge methods used to study these interactions. It highlights recent advancements such as 3D co-culture systems, single-cell and spatial omics technologies, that have enhanced the understanding of CCIs. Additionally, it summarizes the practical applications of CCI research in advancing cardiovascular therapies, offering potential solutions for treating heart disease by targeting intercellular communication.

Abstract This study investigated the possible mechanisms of microRNA-124a on the differentiation of bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanism. β-Thiol ethanol induced Notch1 mRNA expression, microRNA-124a inhibitor reduced the effects of β-thiol ethanol on Notch1 mRNA expression in BMSCs. Baicalin induced Hes1 mRNA expression, and microRNA-124a inhibitor reduced the effects of baicalin on Hes1 mRNA expression in BMSCs. Si-Notch1 suppressed Hes1 mRNA expression in BMSCs. Baicalin increased the effects of Notch1 on Hes1 mRNA expression in BMSCs. Si-Notch1 increased cell growth of BMSCs. Baicalin reduced the effects of si-Notch1 on cell growth and the differentiation of BMSCs. We demonstrated that microRNA-124a promoted the differentiation of BMSCs into neurons through Notch/Hes1 signal pathway.

Abstract Adult patients with patent ductus arteriosus (PDA) have a higher procedural risk during transcatheter PDA closures than infants and children. Limited information is available on transcatheter occlusion in patients with PDA and concomitant comorbidities such as leukemia. We report a case of a 32‐year‐old man with chronic myeloid leukemia who developed sudden hemoptysis during PDA catheter closure. Immediate treatment involved embolization of a bleeding bronchial artery with polyvinyl alcohol particles. The patient successfully underwent PDA closure and hematopoietic cell transplantation 3 months later. This case emphasizes the importance of evaluating fragile vasculature in patients with comorbid chronic diseases.

Abstract Background Scrub typhus is an acute infectious disease caused by Orientia tsutsugamushi. Guillain–Barre syndrome (GBS) is an autoimmune-mediated peripheral neuropathy with a frequent history of prodromal infections, but GBS associated with scrub typhus is very rare. Case presentation We report a 51-year-old male patient who developed dysarthria and peripheral facial paralysis following the cure of scfrub typhus. CSF examination and electrophysiological findings suggested a diagnosis of GBS. After treatment with intravenous immunoglobulin, the patient’s neurological condition improved rapidly. Conclusions Scrub typhus infection is likely to be a potential predisposing factor in GBS, while scrub typhus-associated GBS has a favorable prognosis.

Abstract During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Dilated cardiomyopathy (DCM) is one of the main causes of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation worldwide. Mutations in dozens of cardiac genes have been connected to the development of DCM including the Troponin T2 gene (TNNT2). Here, we generated a human induced pluripotent stem cells (hiPSCs) from a DCM patient with a familial history that carries a missense mutation in TNNT2. The hiPSCs show typical morphology of pluripotent stem cells, expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers.

Alternative splicing is a complex gene regulatory process that distinguishes itself from canonical splicing by rearranging the introns and exons of an immature pre-mRNA transcript. This process plays a vital role in enhancing transcriptomic and proteomic diversity from the genome. Alternative splicing has emerged as a pivotal mechanism governing complex biological processes during both heart development and the development of cardiovascular diseases. Multiple alternative splicing factors are involved in a synergistic or antagonistic manner in the regulation of important genes in relevant physiological processes. Notably, circular RNAs have only recently garnered attention for their tissue-specific expression patterns and regulatory functions. This resurgence of interest has prompted a reevaluation of the topic. Here, we provide an overview of our current understanding of alternative splicing mechanisms and the regulatory roles of alternative splicing factors in cardiovascular development and pathological process of different cardiovascular diseases, including cardiomyopathy, myocardial infarction, heart failure and atherosclerosis.

Mitochondrial diseases are disorders caused primarily by mutations in mitochondrial DNA, with the mitochondrial 3243A > G (m.3243A > G) mutation being one of the most common pathogenic mutations. Here, a pluripotent stem cell line with high m.3243A > G mutation load was generated by reprogramming the skin fibroblasts from a patient with mitochondrial disease. This cell line exhibited pluripotency, multilineage differentiation potential and normal karyotype, representing a valuable cell resource for studying the pathogenesis of mitochondrial diseases and screening drugs.

Abstract Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

Genetic diversity is crucial for determining the evolutionary potential of a species and is essential for developing optimal conservation strategies. The impact of habitat fragmentation on the genetic diversity of food-deceptive orchids seems to be unpredictable because of their specialized seed and pollen dispersal mechanisms. The habitat of deceptive Cypripedium flavum was severely fragmented during the past half century. This study investigated the genetic diversity and structure of seven fragmented Cypripedium flavum populations in Shangrila County using AFLP markers. A total of 376 alleles were identified, with a range of 70 to 81 alleles per locus. The species exhibited considerable genetic diversity, as evidenced by an average Nei’s gene diversity (H) of 0.339 and a Shannon’s information index (I) of 0.505, with all loci being polymorphic. Based on Molecular Variance (AMOVA), 8.75% of the genetic differentiation was found among populations, while the remaining 91.25% of genetic variation occurred within populations. Population structure analysis revealed that the C. flavum germplasm can be categorized into 2 distinct groups, among which there was significant gene flow. Despite habitat fragmentation, C. flavum still retained a high level of genetic diversity, and the substantial gene flow (5.0826) is a key factor in maintaining the genetic diversity. These findings offer valuable insights for the conservation and potential use of C. flavum genetic resources.

Salvia leucantha is a perennial herb of the genus Salvia in the family Labiatae, which has a wide range of biological activities, mainly including inhibition of acetylcholinesterase, antibacterial, and anti-inflammatory activity. To explore the protective effects and mechanism of action of S. leucantha on Alzheimer’s disease (AD), the anti-AD activity of SLE (extracts of S. leucantha) was determined by using a transgenic Caenorhabditis elegans (C. elegans) model (CL4176). Analyses included paralysis assay, phenotypic experiments, transcriptome sequencing, RNA interference (RNAi), heat shock assays, and gas chromatography-mass spectrometry (GC-MS). SLPE (S. leucantha petroleum ether extract) could significantly delay CL4176 paralysis and extend the longevity of C. elegans N2 without harmful effects. A total of 927 genes were significantly changed by SLPE treatment in C. elegans, mainly involving longevity regulatory pathways—nematodes, drug metabolism—cytochrome P450, and glutathione metabolic pathways. RNAi showed that SLPE exerted its anti-AD activity through up-regulation of the gene gst-5; the most abundant compound in SLPE analyzed by GC-MS was 2,4-Di-tert-butylphenol (2,4-DTBP), and the compound delayed nematode paralysis. The present study suggests that active components in S. leucantha may serve as new-type anti-AD candidates and provide some insights into their biological functions.

Mitochondrial diseases are a heterogeneous group of inherited disorders characterized by mitochondrial dysfunction, and these diseases are often severe or even fatal. Mitochondrial diseases are often caused by mitochondrial DNA mutations. Currently, there is no curative treatment for patients with pathogenic mitochondrial DNA mutations. With the rapid development of traditional gene editing technologies, such as zinc finger nucleases and transcription activator-like effector nucleases methods, there has been a search for a mitochondrial gene editing technology that can edit mutated mitochondrial DNA; however, there are still some problems hindering the application of these methods. The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing. In this paper, we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.

Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by diastolic dysfunction, which affects cardiac systolic function. We successfully established human induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells of 24-year-old male with restrictive cardiomyopathy (RCM). The patient-derived hiPSCs carried heterozygous mutation of CRYAB gene (c.326A > G, p.D109G), which was consistent with clinical whole exon sequencing results. We confirmed the pluripotency, multipotential differentiation and karyotype of hiPSCs. The hiPSCs will be useful for studying the pathogenesis of RCM caused by CRYAB (c.326A > G) mutation.

Low-temperature sintering Ag technology is a feasible approach employed in power electron devices. In this study, the influence of the different amounts (0, 0.03, 0.05, 0.07, 0.10, 0.20 wt%) of silicon carbide nanowires (SiC NWs) on the properties and microstructure of micro-Ag paste sintered at 250 °C without pressure has been investigated. The results exhibit that the bonding strength of the Ag-SiC joint reaches a maximum of 43.57 MPa after doping 0.07 wt% SiC NWs, with an increase of 13 % compared with pure Ag joint. This enhancement mechanism can be owed to the Orowan mechanism and the pinning effect of SiC NWs, which nail at grain boundaries that will restrain the dislocation motion of Ag grains. Meanwhile, the electrical resistivity of Ag-0.07SiC shows a minimum value of 5.20 μΩ cm, approximately 10.65 % lower than pure Ag joint. This is attributed to the well-sintered Ag network and the bridging effect of SiC NWs distributed in Ag particles. Thus, incorporating appropriate content of SiC NWs into micro-Ag paste can strengthen the mechanical performance and electrical conductivity of sintered Ag joint. It is hoped that this research could develop a new micro-Ag paste with outstanding properties that could be employed in high-power electronic devices.

Carbon dioxide (CO2) is being considered for use to enhance oil recovery and resource utilization and storage, with wide technical adaptability. In this paper, a numerical simulation method is used to study the adaptability of CO2 huff and puff in shale reservoirs. A fluid model introduces the nanoconfinement effect and reflects the nanoconfinement effect using the fluid p–T phase diagram. This method uses local grid refinement and changes the permeability near the grid to characterize the reservoir reconstruction volume (SRV) fracture network while considering the CO2 diffusion effect. The results indicate that by using the incremental recovery rate and oil change rate as references, adaptive charts can be obtained for different Kf/Km and oil saturation. When Kf/Km is 1000 and the increase in the CO2 recovery rate reaches 1.5%, the lower limit of oil saturation is 0.54. When Kf/Km is 1000 and the increase in the CO2 recovery rate reaches 2%, the lower limit of oil saturation is 0.57. When the oil saturation is 0.5 and the CO2 huff and puff oil change rate reaches 0.3, the lower limit of Kf/Km is 700. Finally, when the oil saturation is 0.548 and the CO2 huff and puff oil change rate reaches 0.6, the lower limit of Kf/Km is 10. The research results are significant and can guide the design and application of on-site CO2 throughput test plans.