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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.

Abstract Ischaemia of the heart and limbs attributable to compromised blood supply is a major cause of mortality and morbidity. The mechanisms of functional angiogenesis remain poorly understood, however. Here we show that FNIP1 plays a critical role in controlling skeletal muscle functional angiogenesis, a process pivotal for muscle revascularization during ischemia. Muscle FNIP1 expression is down-regulated by exercise. Genetic overexpression of FNIP1 in myofiber causes limited angiogenesis in mice, whereas its myofiber-specific ablation markedly promotes the formation of functional blood vessels. Interestingly, the increased muscle angiogenesis is independent of AMPK but due to enhanced macrophage recruitment in FNIP1-depleted muscles. Mechanistically, myofiber FNIP1 deficiency induces PGC-1α to activate chemokine gene transcription, thereby driving macrophage recruitment and muscle angiogenesis program. Furthermore, in a mouse hindlimb ischemia model of peripheral artery disease, the loss of myofiber FNIP1 significantly improved the recovery of blood flow. Thus, these results reveal a pivotal role of FNIP1 as a negative regulator of functional angiogenesis in muscle, offering insight into potential therapeutic strategies for ischemic diseases.

Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) represent a promising source of human ECs urgently needed for the study of cardiovascular disease mechanisms, cell therapy, and drug screening. This study aims to explore the function and regulatory mechanism of the miR-148/152 family consisting of miR-148a, miR-148b, and miR-152 in hPSC-ECs, so as to provide new targets for improving EC function during the above applications. In comparison with the wild-type (WT) group, miR-148/152 family knockout (TKO) significantly reduced the endothelial differentiation efficiency of human embryonic stem cells (hESCs), and impaired the proliferation, migration, and capillary-like tube formatting abilities of their derived ECs (hESC-ECs). Overexpression of miR-152 partially restored the angiogenic capacity of TKO hESC-ECs. Furthermore, the mesenchyme homeobox 2 (MEOX2) was validated as the direct target of miR-148/152 family. MEOX2 knockdown resulted in partial restoration of the angiogenesis ability of TKO hESC-ECs. The Matrigel plug assay further revealed that the in vivo angiogenic capacity of hESC-ECs was impaired by miR-148/152 family knockout, and increased by miR-152 overexpression. Thus, the miR-148/152 family is crucial for maintaining the angiogenesis ability of hPSC-ECs, and might be used as a target to enhance the functional benefit of EC therapy and promote endogenous revascularization.

Abstract Background Cardiac epicardium hemangiomas are exceedingly rare; however, they can cause significant hemodynamic impairment and large pericardial effusions. On rare occasion, cardiac tumors coexist with malformations of the heart. Case presentation We present the case of a 10-month-old female infant with a rare cardiac surface hemangioma coexisting with malformations of the heart. It revealed an atrial septal defect (ASD) coexisting with an abnormal occupying lesion with high echogenicity. It was 35*12*9 mm in size and was found in the anterior atrioventricular junction to the posterior atrioventricular junction at the bottom of the ventricular septum by transthoracic echocardiography. We performed surgical treatment of the atrial septal defect and performed biopsy with the occupying lesion. The histopathological examination reported a benign tumor as hemangioma. As far as we know, this is the first case in which cardiac surface hemangioma was found to coexist with an atrial septal defect. Conclusions Cardiac epicardium hemangiomas is a rare solid tumor of the heart. If the mass is impossible to resect and does not cause hemodynamic impairment, only mass biopsy is possible.

Abstract Exploring the functions of human-specific genes (HSGs) is challenging due to the lack of a tractable genetic model system. Testosterone is essential for maintaining human spermatogenesis and fertility, but the underlying mechanism is unclear. Here, we identified Cancer/Testis Antigen gene family 47 (CT47) as an essential regulator of human-specific spermatogenesis by stabilizing arginine methyltransferase 5 (PRMT5). A humanized mouse model revealed that CT47 functions to arrest spermatogenesis by interacting with and regulating CT47/PRMT5 accumulation in the nucleus during the leptotene/zygotene-to-pachytene transition of meiosis. We demonstrate that testosterone induces nuclear depletion of CT47/PRMT5 and rescues leptotene-arrested spermatocyte progression in humanized testes. Loss of CT47 in human embryonic stem cells (hESCs) by CRISPR/Cas9 led to an increase in haploid cells but blocked the testosterone-induced increase in haploid cells when hESCs were differentiated into haploid spermatogenic cells. Moreover, CT47 levels were decreased in nonobstructive azoospermia. Together, these results established CT47 as a crucial regulator of human spermatogenesis by preventing meiosis initiation before the testosterone surge.

Abstract Background Endothelial cells are located in the inner lumen of blood and lymphatic vessels and exhibit the capacity to form new vessel branches from existing vessels through a process called angiogenesis. This process is energy intensive and tightly regulated. Glycolysis is the main energy source for angiogenesis. Retinoic acid (RA) is an active metabolite of vitamin A and exerts biological effects through its receptor retinoic acid receptor (RAR). In the clinic, RA is used to treat acne vulgaris and acute promyelocytic leukemia. Emerging evidence suggests that RA is involved in the formation of the vasculature; however, its effect on endothelial cell angiogenesis and metabolism is unclear. Methods Our study was designed to clarify the abovementioned effect with human embryonic stem cell-derived endothelial cells (hESC-ECs) employed as a cell model. Results We found that RA inhibits angiogenesis, as manifested by decreased proliferation, migration and sprouting activity. RNA sequencing revealed general suppression of glycometabolism in hESC-ECs in response to RA, consistent with the decreased glycolytic activity and glucose uptake. After screening glycometabolism-related genes, we found that fructose-1,6-bisphosphatase 1 (FBP1), a key rate-limiting enzyme in gluconeogenesis, was significantly upregulated after RA treatment. After silencing or pharmacological inhibition of FBP1 in hESC-ECs, the capacity for angiogenesis was enhanced, and the inhibitory effect of RA was reversed. ChIP-PCR demonstrated that FBP1 is a target gene of RAR. When hESC-ECs were treated with the RAR inhibitor BMS493, FBP1 expression was decreased and the effect of RA on angiogenesis was partially blocked. Conclusions The inhibitory role of RA in glycometabolism and angiogenesis is RAR/FBP1 dependent, and FBP1 may be a novel therapeutic target for pathological angiogenesis.

Abstract Engineered cardiac tissues (ECTs) derived from human induced pluripotent stem cells (hiPSCs) are viable alternatives for cardiac repair, patient‐specific disease modeling, and drug discovery. However, the immature state of ECTs limits their clinical utility. The microenvironment fabricated using 3D scaffolds can affect cell fate, and is crucial for the maturation of ECTs. Herein, the authors demonstrate an electric‐field‐driven (EFD) printed 3D highly ordered microstructure with cell feature size to promote the maturation of ECTs. The simulation and experimental results demonstrate that the EFD jet microscale 3D printing overcomes the jet repulsion without any prior requirements for both conductive and insulating substrates. Furthermore, the 3D highly ordered microstructures with a fiber diameter of 10–20 µm and spacing of 60–80 µm have been fabricated by maintaining a vertical jet, achieving the largest ratio of fiber diameter/spacing of 0.29. The hiPSCs‐derived cardiomyocytes formed ordered ECTs with their sarcomere growth along the fiber and developed synchronous functional ECTs inside the 3D‐printed scaffold with matured calcium handling compared to the 2D coverslip. Therefore, the EFD jet 3D microscale printing process facilitates the fabrication of scaffolds providing a suitable microenvironment to promote the maturation of ECTs, thereby showing great potential for cardiac tissue engineering.

ObjectivesBy reviewing the diagnostic process for adolescents with coarctation of the aorta (CoA) in our institution, we analyzed the reasons for delayed diagnosis of CoA. We also proposed a diagnostic protocol to improve the detection rate of CoA.MethodsIn this retrospective study, we included 48 patients aged 12–18 years who were diagnosed with CoA in our hospital from January 2000 to November 2022. Clinical data from involved cases in local hospitals and our institution were collected.ResultsAll patients had blood pressure (BP) measurements in upper and lower extremities in our institution. They all had hypertension, 29 (60.4%) of whom had known histories of the same. BP in the upper limbs of 47 (97.9%) patients was ≥20 mmHg higher than that in the lower limbs, and BP in the upper limb of 1 (2.1%) patient was greater than 0 and less than 20 mmHg than that in the lower limb. Echocardiography (ECHO) was performed in all patients, computed tomography (CT) or magnetic resonance imaging (MRI) was performed in 44 patients (91.7%). There were 38 (79.2%) patients who visited local hospitals. Among them, a total of 20 (52.6%) patients had their right upper extremity BP measured, 18 (47.4%) only had their left upper extremity BP measured, and 16 (42.1%) had their lower extremity BP measured. ECHO was performed in 27 (56.2%) patients and CT/MRI was performed in 18 (37.5%) patients. The detection rate for CT/MRI was 100%, and those of ECHO were 72.9% and 18.5% at our institution and a local hospital, respectively. Forty-eight (100%) and 23 (60.5%) patients were detected in our institution and local hospitals (P

BackgroundRight ventricular outflow tract (RVOT) stenting seems to be suggested as a promising treatment option and an alternative to modified Blalock-Taussig shunt (mBTS) in the initial palliation of patients with Fallot-type lesions in recent years. This study sought to assess the effect of RVOT stenting on the growth of the pulmonary artery (PA) in patients with Tetralogy of Fallot (TOF).MethodsRetrospective review analyzing 5 patients with Fallot-type congenital heart disease with small pulmonary arteries who underwent palliative with RVOT stenting and 9 patients underwent modified Blalock-Taussig shunt within 9 years period. Differential left PA (LPA) and right PA (RPA) growth was measured by Cardiovascular Computed Tomography Angiography (CTA).ResultsRVOT stenting improved arterial oxygen saturation from median of 60% (interquartile range [IQR]: 37% to 79%) to 95% (87.5% to 97.5%) (p = 0.028). The LPA diameter Z-score improved from −2.843 (−3.51–2.037) to −0.78 (−2.3305–0.19) (p = 0.03), the RPA diameter Z-score improved from median −2.843 (−3.51–2.037) to −0.477 (−1.1145–0.459) (p = 0.002), the Mc Goon ratio increased from median 1 (0.8–1.105) to 1.32 (1.25–1.98) (p = 0.017). There were no procedural complications and all 5 patients have undergone final repair in the RVOT stent group. In the mBTS group, the LPA diameter Z-score improved from −1.494 (−2.242–0.6135) to −0.396 (−1.488–1.228) (p = 0.15), the RPA diameter Z-score improved from median −1.328 (−2.036–0.838) to 0.088 (−0.486–1.223) (p = 0.007), and there were 5 patients occur different complications and 4 patients was not attained the standards of final surgical repair.ConclusionRVOT stenting, compared with mBTS, seems to better promote pulmonary artery growth, improve arterial oxygen saturations, and have less procedure complications in patients with TOF who being absolute contraindicated for primary repair due to high risks.

N6-methyladenosine (m6A), as the most abundant modification of mammalian messenger RNAs, is essential for tissue development and pathogenesis. However, the biological significance of m6A methylation in cardiac differentiation and development remains largely unknown. Here, we identify that the downregulation of m6A demethylase ALKBH5 is responsible for the increase of m6A methylation and cardiomyocyte fate determination of human embryonic stem cells (hESCs) from mesoderm cells (MESs). In contrast, ALKBH5 overexpression remarkably blocks cardiomyocyte differentiation of hESCs. Mechanistically, KDM5B and RBBP5, the components of H3K4 modifying enzyme complexes, are identified as downstream targets for ALKBH5 in cardiac-committed hESCs. Loss of function of ALKBH5 alters the expression of KDM5B and RBBP5 through impairing stability of their mRNAs, which in turn promotes the transcription of GATA4 by enhancing histone H3 Lys4 trimethylation (H3K4me3) at the promoter region of GATA4. Taken together, we reveal a previously unidentified role of m6A demethylase ALKBH5 in determining cardiac lineage commitment of hESCs.

Cryptococcal meningitis is a common fungal infection of the central nervous system with high mortality and disability rates. A prominent clinical manifestation is persistent and severe cranial hypertension, which is one of the most critical outcome determinants in patients with cryptococcal meningoencephalitis. Herein, we report and discuss a case of cryptococcal meningitis treated by an inadequate course of medical therapy and placement of a ventriculoperitoneal shunt in a patient who survived for more than 10 years.

Due to different nucleotide preferences at target sites, no single Cas9 is capable of editing all sequences. Thus, this highlights the need to establish a Cas9 repertoire covering all sequences for efficient genome editing. Cas9s with simple protospacer adjacent motif (PAM) requirements are particularly attractive to allow for a wide range of genome editing, but identification of such Cas9s from thousands of Cas9s in the public database is a challenge. We previously identified PAMs for 16 SaCas9 orthologs. Here, we compared the PAM-interacting (PI) domains in these orthologs and found that the serine residue corresponding to SaCas9 N986 was associated with the simple NNGG PAM requirement. Based on this discovery, we identified five additional SaCas9 orthologs that recognize the NNGG PAM. We further identified three amino acids that determined the NNGG PAM requirement of SaCas9. Finally, we engineered Sha2Cas9 and SpeCas9 to generate high-fidelity versions of Cas9s. Importantly, these natural and engineered Cas9s displayed high activities and distinct nucleotide preferences. Our study offers a new perspective to identify SaCas9 orthologs with NNGG PAM requirements, expanding the Cas9 repertoire.

Myocardial infarction (MI) is a common cardiovascular disease caused by permanent loss of cardiomyocytes and the formation of scar tissue due to myocardial ischemia. Mammalian cardiomyocytes lose their ability to proliferate almost completely in adulthood and are unable to repair the damage caused by MI. Therefore, transplantation of exogenous cells into the injured area for treatment becomes a promising strategy. Pluripotent stem cells (PSCs) have the ability to proliferate and differentiate into various cellular populations indefinitely, and pluripotent stem cell-derived cardiomyocytes (PSC-CMs) transplanted into areas of injury can compensate for part of the injuries and are considered to be one of the most promising sources for cell replacement therapy. However, the low transplantation rate and survival rate of currently transplanted PSC-CMs limit their ability to treat MI. This article focuses on the strategies of current research for improving the therapeutic efficacy of PSC-CMs, aiming to provide some inspiration and ideas for subsequent researchers to further enhance the transplantation rate and survival rate of PSC-CMs and ultimately improve cardiac function.

Pulmonary sequestration with congenital heart disease is a rare congenital malformation. Herein, we report a 19-month-old toddler diagnosed with right lower pulmonary sequestration, right pulmonary artery dysplasia, right lower pulmonary venous ectopic drainage, and a right-sided heart with an atrial septal defect. The pulmonary sequestration had a rare blood supply, such as confluent arteries with the renal vessels draining into the hepatic veins. Arterial embolization and atrial defect closure were used to treat the rare congenital malformation with satisfactory results.

Abstract Clustered regularly interspaced short palindromic repeat (CRISPR)/SaCas9 is the most popular tool for in vivo genome editing due to its high efficiency and small genome. The authors previously developed four SaCas9 orthologs as genome‐editing tools. Here, to expand the targeting scope, they investigate the diversity of protospacer adjacent motifs (PAMs) by screening a list of 16 SaCas9 orthologs, twelve of which display editing activity in mammalian cells. They recognize five types of PAMs: NNGRRT, NNGRRR, NNGRC, NNGA, and NNGR. Importantly, SchCas9 recognizes the simple NNGR PAM, representing the most relaxed PAM preference of compact Cas9s to date. It is further demonstrated that SchCas9 enables efficient genome editing in multiple human cell lines. Altogether, these compact Cas9 tools offer a new option for both basic research and clinical applications.

IntroductionComplex ectopic drainage of body veins is a rare congenital disease. Its preoperative diagnosis and surgical choice can be considerable challenges.Case SummaryA 5-year-old patient was diagnosed precisely by preoperative transthoracic echocardiography, computed tomography (CT), three-dimensional (3D) reconstruction, and three-dimensional (3D) printing of the heart and great blood vessels. The operation was performed successfully using flexible intraoperative intubation strategies.Conclusion3D printing technology can assist in the formulation of surgical protocols for complex body vein ectopic drainage. Flexible intubation strategies can increase the success of the operation.

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.