Accelerated discovery and miniaturization of novel single-stranded cytidine deaminases.

Cytidine base editors (CBEs) hold significant potential in genetic disease treatment and in breeding superior traits into animals. However, their large protein sizes limit their delivery by adeno-associated virus (AAV), given its packing capacity of <4.7 kb.

A wearable iontophoresis enables dual-responsive transdermal delivery for atopic dermatitis treatment.

Atopic dermatitis is a chronic, inflammation skin disease that remains a major public health challenge. The current drug-loading hydrogel dressings offer numerous benefits with enhanced loading capacity and a moist-rich environment. However, their development is still limited by the accessibility of a suitable driven source outside the clinical environment for precise control over transdermal delivery kinetics.

Mfn2, Mfn2, and Mfn2 mutations drive Charcot-Marie-Tooth type 2A disease by inducing apoptosis and mitochondrial oxidative phosphorylation damage.

Charcot-Marie-Tooth type 2A (CMT2A) is a single-gene motor sensory neuropathy caused by Mfn2 mutation. It is generally believed that CMT2A involves mitochondrial fusion disruption. However, how Mfn2 mutation mediates the mitochondrial membrane fusion loss and its further pathogenic mechanisms remain unclear.

Effective inhibition of PDCoV infection in chimeric APN gene-edited neonatal pigs.

Unlabelled: Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, is a serious threat to piglets and has zoonotic potential. Here, we aimed to further explore the role of aminopeptidase N (APN) as a receptor for PDCoV and test the inhibitory effect of a chimeric APN protein strategy on PDCoV infection. PK-15 cells and LLC-PK1 cells expressing chimeric APN were selected and infected with PDCoV.

Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection.

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance.

Mechanism, structural and functional insights into nidovirus-induced double-membrane vesicles.

During infection, positive-stranded RNA causes a rearrangement of the host cell membrane, resulting in specialized membrane structure formation aiding viral genome replication. Double-membrane vesicles (DMVs), typical structures produced by virus-induced membrane rearrangements, are platforms for viral replication. Nidoviruses, one of the most complex positive-strand RNA viruses, have the ability to infect not only mammals and a few birds but also invertebrates.

MYH7 R453C induced cardiac remodelling via activating TGF-β/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways.

Hypertrophic cardiomyopathy (HCM) is a monogenic cardiac disorder commonly induced by sarcomere gene mutations. However, the mechanism for HCM is not well defined. Here, we generated transgenic MYH7 R453C and MYH6 R453C piglets and found both developed typical cardiac hypertrophy.

Yeast β-glucan promotes antiviral type I interferon response via dectin-1.

Pseudorabies virus (PRV), an alphaherpesvirus, is a neglected zoonotic pathogen. Dectin-1 sensing of β-glucan (BG) induces trained immunity, which can possibly form a new strategy for the prevention of viral infection. However, alphaherpesvirus including PRV have received little to no investigation in the context of trained immunity.

miR-26a-5p inhibits the proliferation of psoriasis-like keratinocytes and by dual interference with the CDC6/CCNE1 axis.

Psoriasis is a chronic inflammatory proliferative dermatological ailment that currently lacks a definitive cure. Employing data mining techniques, this study identified a collection of substantially downregulated miRNAs (top 10). Notably, 32 targets were implicated in both the activation of the IL-17 signaling pathway and cell cycle dysregulation.

Regulatory Non-Coding RNAs during Porcine Viral Infections: Potential Targets for Antiviral Therapy.

Pigs play important roles in agriculture and bio-medicine; however, porcine viral infections have caused huge losses to the pig industry and severely affected the animal welfare and social public safety. During viral infections, many non-coding RNAs are induced or repressed by viruses and regulate viral infection. Many viruses have, therefore, developed a number of mechanisms that use ncRNAs to evade the host immune system.

An integrative analysis of genotype-phenotype correlation in Charcot Marie Tooth type 2A disease with MFN2 variants: A case and systematic review.

Dominant genetic variants in the mitofusin 2 (MFN2) gene lead to Charcot-Marie-Tooth type 2A (CMT2A), a neurodegenerative disease caused by genetic defects that directly damage axons. In this study, we reported a proband with a pathogenic variant in the GTPase domain of MFN2, c.494A > G (p.

Large-Scale CRISPR Screen of LDLR Pathogenic Variants.

Familial hypercholesterolemia (FH) is a frequently occurring genetic disorder that is linked to early-onset cardiovascular disease. If left untreated, patients with this condition can develop severe cardiovascular complications. Unfortunately, many patients remain undiagnosed, and even when diagnosed, the treatment is often not optimal.

Transmissible Gastroenteritis Virus: An Update Review and Perspective.

Transmissible gastroenteritis virus (TGEV) is a member of the alphacoronavirus genus, which has caused huge threats and losses to pig husbandry with a 100% mortality in infected piglets. TGEV is observed to be recombining and evolving unstoppably in recent years, with some of these recombinant strains spreading across species, which makes the detection and prevention of TGEV more complex. This paper reviews and discusses the basic biological properties of TGEV, factors affecting virulence, viral receptors, and the latest research advances in TGEV infection-induced apoptosis and autophagy to improve understanding of the current status of TGEV and related research processes.

Erratum: HMEJ-mediated site-specific integration of a myostatin inhibitor increases skeletal muscle mass in porcine.

[This corrects the article DOI: 10.1016/j.omtn.

An integrated Mg battery-powered iontophoresis patch for efficient and controllable transdermal drug delivery.

Wearable transdermal iontophoresis eliminating the need for external power sources offers advantages for patient-comfort when deploying epidermal diseases treatments. However, current self-powered iontophoresis based on energy harvesters is limited to support efficient therapeutic administration over the long-term operation, owing to the low and inconsistent energy supply. Here we propose a simplified wearable iontophoresis patch with a built-in Mg battery for efficient and controllable transdermal delivery.

Lp-PLA (Lipoprotein-Associated Phospholipase A) Deficiency Lowers Cholesterol Levels and Protects Against Atherosclerosis in Rabbits.

Background: Elevated plasma Lp-PLA (lipoprotein-associated phospholipase A) activity is closely associated with an increased risk of cardiovascular events. However, whether and how Lp-PLA is directly involved in the pathogenesis of atherosclerosis is still unclear. To examine the hypothesis that Lp-PLA could be a potential preventative target of atherosclerosis, we generated Lp-PLA knockout rabbits and investigated the pathophysiological functions of Lp-PLA.

Porcine Epidemic Diarrhea Virus: An Updated Overview of Virus Epidemiology, Virulence Variation Patterns and Virus-Host Interactions.

The porcine epidemic diarrhea virus (PEDV) is a member of the coronavirus family, causing deadly watery diarrhea in newborn piglets. The global pandemic of PEDV, with significant morbidity and mortality, poses a huge threat to the swine industry. The currently developed vaccines and drugs are only effective against the classic GI strains that were prevalent before 2010, while there is no effective control against the GII variant strains that are currently a global pandemic.

MYBPC3 deficiency in cardiac fibroblasts drives their activation and contributes to fibrosis.

Genetic mutations in the MYBPC3 gene encoding cardiac myosin binding protein C (cMyBP-C) are the most common cause of hypertrophic cardiomyopathy (HCM). Myocardial fibrosis (MF) plays a critical role in the development of HCM. However, the mechanism for mutant MYBPC3-induced MF is not well defined.

Lactate facilitates classical swine fever virus replication by enhancing cholesterol biosynthesis.

An emerging topic in virology is that viral replication is closely linked with the metabolic reprogramming of host cells. Understanding the effects of reprogramming host cell metabolism due to classical swine fever virus (CSFV) infection and the underling mechanisms would facilitate controlling the spread of classical swine fever (CSF). In the current study, we found that CSFV infection enhanced aerobic glycolysis in PK-15 cells.

Generation of APN-chimeric gene-edited pigs by CRISPR/Cas9-mediated knock-in strategy.

The prevalence of porcine enteric coronaviruses (PECs), including transmissible gastroenteritis virus (TGEV), swine acute diarrhea syndrome coronavirus (SADS-CoV), porcine delta coronavirus (PDCoV), and porcine epidemic diarrhea virus (PEDV), poses a serious threat to animal and public health. Here, we aimed to further optimize the porcine aminopeptidase N (pAPN) gene editing strategy to explore the balance between individual antiviral properties and the biological functions of pAPN in pigs. Finally, APN-chimeric gene-edited pigs were produced through a CRISPR/Cas9-mediated knock-in strategy.

Clostridium butyricum and Bifidobacterium pseudolongum Attenuate the Development of Cardiac Fibrosis in Mice.

Cardiac fibrosis is an integral aspect of every form of cardiovascular diseases, which is one of the leading causes of death worldwide. It is urgent to explore new effective drugs and treatments. In this paper, transverse aortic constriction (TAC)-induced cardiac fibrosis was significantly alleviated by a cocktail of antibiotics to clear the intestinal flora, indicating that the gut microbiota was associated with the disease process of cardiac fibrosis.

Advance of genetically modified pigs in xeno-transplantation.

As the standard of living improves, chronic diseases and end-stage organ failure have been a regular occurrence in human beings. Organ transplantation has become one of the hopes in the fight against chronic diseases and end-stage organ failure. However, organs available for transplantation are far from sufficient to meet the demand, leading to a major organ shortage crisis.

Correction: Wang et al. TERT Promoter Revertant Mutation Inhibits Melanoma Growth through Intrinsic Apoptosis. 2022, , 141.

The authors would like to make the following correction to the published paper [...