Anti-PD-1 exacerbates bleomycin-induced lung injury in mice via Caspase-3/GSDME-mediated pyroptosis.

Immune checkpoint inhibitors (ICIs) have significant therapeutic effects but can also cause fatal lung injury. However, the lack of mouse animal models of ICI-related lung injury (ICI-LI) has limited the in-depth exploration of its pathogenesis. In clinical practice, underlying lung diseases increase the risk of lung injury.

Evolved cytidine and adenine base editors with high precision and minimized off-target activity by a continuous directed evolution system in mammalian cells.

Continuous directed evolution of base editors (BEs) has been successful in bacteria cells, but not yet in mammalian cells. Here, we report the development of a Continuous Directed Evolution system in Mammalian cells (CDEM). CDEM enables the BE evolution in a full-length manner with Cas9 nickase.

[Advances in base editing systems].

Programmable nucleases-based genome editing systems offer several advantages, such as high editing efficiency, high product purity, and fewer editing by-products. They have been widely used in biopharmaceutical research and crop engineering. Given the diverse needs for research and application, developing functional base editors has become a major focus in the field of genome editing.

Biocytin-Labeling in Whole-Cell Recording: Electrophysiological and Morphological Properties of Pyramidal Neurons in CYLD-Deficient Mice.

Biocytin, a chemical compound that is an amide formed from the vitamin biotin and the amino acid L-lysine, has been used as a histological dye to stain nerve cells. Electrophysiological activity and morphology are two key characteristics of neurons, but revealing both the electrophysiological and morphological properties of the same neuron is challenging. This article introduces a detailed and easy-to-operate procedure for single-cell labeling in combination with whole-cell patch-clamp recording.

Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study.

The roles of Rho GTPases in various types of cancer have been extensively studied, but the research of Rho guanine nucleotide exchange factors (GEFs) in cancer is not comprehensive. Rho guanine nucleotide exchange factor 6 (ARHGEF6) is an important member of the Rho GEFs family involved in cytoskeletal rearrangement, and it has not been investigated in acute myeloid leukemia (AML). Our research showed that the expression of ARHGEF6 was mainly higher in AML cell lines, meanwhile, was highest in the samples from patients with AML compared to other cancer types.

Cas9-orthologue-mediated cytosine and adenine base editors recognizing NNAAAA PAM sequences.

CRISPR/Cas9 system has been applied as an effective genome-targeting technology. By fusing deaminases with Cas9 nickase (nCas9), various cytosine and adenine base editors (CBEs and ABEs) have been successfully developed that can efficiently induce nucleotide conversions and install pathogenic single nucleotide variants (SNVs) in cultured cells and animal models. However, the applications of BEs are frequently limited by the specific protospacer adjacent motif (PAM) sequences and protein sizes.

Resistance-switchable conjugated polyrotaxane for flexible high-performance RRAMs.

A representative closely packed conjugated polyrotaxane (CPR1) is synthesized by threading polyaniline (PAN) into β-cyclodextrin (CD) macrocycles and utilized for the first time to construct an RRAM device that exhibits an outstanding resistive switching capability. The CPR1 RRAM device displays remarkable nonvolatile memory performance with an extremely high ON/OFF ratio of 10, the ultra-fast response of 29 ns, excellent reliability and reproducibility, and long-term stability (more than 1 year). The mechanism underlying this resistive switching behavior is understood according to the electric-field-induced proton doping of the PAN core by the CD sheath through hydrogen bonding interactions.

Structure-guided engineering of adenine base editor with minimized RNA off-targeting activity.

Both adenine base editors (ABEs) and cytosine base editors (CBEs) have been recently revealed to induce transcriptome-wide RNA off-target editing in a guide RNA-independent manner. Here we construct a reporter system containing E.coli Hokb gene with a tRNA-like motif for robust detection of RNA editing activities as the optimized ABE, ABEmax, induces highly efficient A-to-I (inosine) editing within an E.

Recyclable low-temperature phase change microcapsules for cold storage.

Recyclable low-temperature phase change microcapsules (LTPCMs) have the potential applications in the short-distance cold chain transportation due to their reliable reusability in cold storage. Herein, LTPCMs are synthesized via in-situ suspension copolymerization of styrene and methyl methacrylate in absence of harm substances, providing the non-crosslinking copolymer shells. n-Dodecane, n-tridecane and n-tetradecane, inducing the microphase separation of non-crosslinking copolymers, are successfully encapsulated to achieve n-do-LTPCMs, n-tri-LTPCMs and n-tetra-LTPCMs, which respectively bear the high phase change enthalpy of 110.

Gramicidin inhibits cholangiocarcinoma cell growth by suppressing EGR4.

Gramicidin is a well-known antibiotic and recently was reported to induced tumour cell death, however, little is understood about the molecular mechanism of gramicidin as a therapeutic agent for solid tumours. Here, we investigated the role of gramicidin in cholangiocarcinoma cells. We found that gramicidin A inhibits cholangiocarcinoma cell growth and induced the necrotic cell death.

YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma.

Background: Dynamic N-methyladenosine (mA) modification was previously identified as a ubiquitous post-transcriptional regulation that affected mRNA homeostasis. However, the mA-related epitranscriptomic alterations and functions remain elusive in human cancer. Here we aim to identify the profile and outcome of mA-methylation in hepatocellular carcinoma (HCC).

Enhanced Switching Ratio and Long-Term Stability of Flexible RRAM by Anchoring Polyvinylammonium on Perovskite Grains.

The ON/OFF ratio and long-term stability are two important issues for flexible organic-inorganic hybrid perovskite (OHP) resistive random access memory (RRAM) for practical applications. In this work, polyvinylammonium (PVAm) is applied to partially replace methylamine ions (MA) to fabricate the stable and flexible polymeric OHP RRAM devices, wherein PVAm acts as nucleation sites and the template for crystalline growth of MAPbI to tune the microscopic perovskite structure. Simultaneously, the multiple perovskite grain interfaces are strengthened through the long-carbochain polymeric backbone, hence producing a continuous and compact perovskite film.

Base pair editing in goat: nonsense codon introgression into FGF5 results in longer hair.

The ability to alter single bases without homology directed repair (HDR) of double-strand breaks provides a potential solution for editing livestock genomes for economic traits, which are often multigenic. Progress toward multiplex editing in large animals has been hampered by the costly inefficiencies of HDR via microinjection of in vitro manipulated embryos. Here, we designed sgRNAs to induce nonsense codons (C-to-T transitions) at four target sites in caprine FGF5, which is a crucial regulator of hair length in mammals.

Efficient generation of goats with defined point mutation (I397V) in GDF9 through CRISPR/Cas9.

The recent emergence of the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9 system has attracted significant attention for its potential to improve traits of agricultural importance. However, most applications in livestock species to date have depended on aberrant DNA repair to generate frameshifting indels. Whether this genomic engineering technique involving homology-dependent repair (HDR) can be used to introduce defined point mutations has been less explored.

Correction: Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers.

[This corrects the article DOI: 10.1371/journal.pone.

Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in More Secondary Hair Follicles and Longer Fibers.

Precision genetic engineering accelerates the genetic improvement of livestock for agriculture and biomedicine. We have recently reported our success in producing gene-modified goats using the CRISPR/Cas9 system through microinjection of Cas9 mRNA and sgRNAs targeting the MSTN and FGF5 genes in goat embryos. By investigating the influence of gene modification on the phenotypes of Cas9-mediated goats, we herein demonstrate that the utility of this approach involving the disruption of FGF5 results in increased number of second hair follicles and enhanced fiber length in Cas9-mediated goats, suggesting more cashmere will be produced.

Multiplex gene editing via CRISPR/Cas9 exhibits desirable muscle hypertrophy without detectable off-target effects in sheep.

The CRISPR/Cas9 system provides a flexible approach for genome engineering of genetic loci. Here, we successfully achieved precise gene targeting in sheep by co-injecting one-cell-stage embryos with Cas9 mRNA and RNA guides targeting three genes (MSTN, ASIP, and BCO2). We carefully examined the sgRNAs:Cas9-mediated targeting effects in injected embryos, somatic tissues, as well as gonads via cloning and sequencing.

Generation of an Oocyte-Specific Cas9 Transgenic Mouse for Genome Editing.

The CRISPR/Cas9 system has been developed as an easy-handle and multiplexable approach for engineering eukaryotic genomes by zygote microinjection of Cas9 and sgRNA, while preparing Cas9 for microinjection is laborious and introducing inconsistency into the experiment. Here, we describe a modified strategy for gene targeting through using oocyte-specific Cas9 transgenic mouse. With this mouse line, we successfully achieve precise gene targeting by injection of sgRNAs only into one-cell-stage embryos.

CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients.

Strategies that enhance the function of T cells are critical for immunotherapy. One negative regulator of T-cell activity is ligand PD-L1, which is expressed on dentritic cells (DCs) or some tumor cells, and functions through binding of programmed death-1 (PD-1) receptor on activated T cells. Here we described for the first time a non-viral mediated approach to reprogram primary human T cells by disruption of PD-1.

CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.

Mutations in the DAX1 locus cause X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH), which manifest with primary adrenal insufficiency and incomplete or absent sexual maturation, respectively. The associated defects in spermatogenesis can range from spermatogenic arrest to Sertoli cell only syndrome. Conclusions from Dax1 knockout mouse models provide only limited insight into AHC/HH disease mechanisms, because mouse models exhibit more extensive abnormalities in testicular development, including disorganized and incompletely formed testis cords with decreased number of peritubular myoid cells and male-to-female sex reversal.

Generation of gene-modified goats targeting MSTN and FGF5 via zygote injection of CRISPR/Cas9 system.

Recent advances in the study of the CRISPR/Cas9 system have provided a precise and versatile approach for genome editing in various species. However, the applicability and efficiency of this method in large animal models, such as the goat, have not been extensively studied. Here, by co-injection of one-cell stage embryos with Cas9 mRNA and sgRNAs targeting two functional genes (MSTN and FGF5), we successfully produced gene-modified goats with either one or both genes disrupted.