Precise deletion, replacement and inversion of large DNA fragments in plants using dual prime editing.

Precise manipulation of genome structural variations holds great potential for plant trait improvement and biological research. Here we present a genome-editing approach, dual prime editing (DualPE), that efficiently facilitates precise deletion, replacement and inversion of large DNA fragments in plants. In our experiments, DualPE enabled the production of specific genomic deletions ranging from ~500 bp to 2 Mb in wheat protoplasts and plants.

CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.

Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).

Caseinate-coated zein nanoparticles as potential delivery vehicles for guavinoside B from guava: Molecular interactions and encapsulation properties.

Guavinoside B (GUB) is a characteristic constituent from guava with strong antioxidant activity; however, its low water solubility limits its utilization. Herein, we investigated the interaction between GUB and zein, a prolamin with self-assembling property, using multiple spectroscopic methods and fabricated GUB-zein-NaCas nanoparticles (GUB-Z-N NPs) via the antisolvent coprecipitation approach. GUB caused fluorescence quenching to zein via the static quenching mechanism.

Ribociclib plus Endocrine Therapy in Early Breast Cancer.

Background: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.

Methods: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.

Fc gamma receptors promote antibody-induced LILRB4 internalization and immune regulation of monocytic AML.

The immune checkpoint leukocyte immunoglobulin-like receptor B4 (LILRB4) is found specifically on the cell surface of acute monocytic leukemia (monocytic AML), an aggressive and common subtype of AML. We have developed a humanized monoclonal IgG LILRB4-blocking antibody (h128-3), which improved immune regulation but reduced cell surface expression of LILRB4 in monocytic AML models by 40-60%. Interestingly, most of this effect was neutralized by mutation of the Fc region of the antibody (h128-3/N297A), which prevents interaction with Fc gamma receptors (FcγRs).

Diatomic iron nanozyme with lipoxidase-like activity for efficient inactivation of enveloped virus.

Enveloped viruses encased within a lipid bilayer membrane are highly contagious and can cause many infectious diseases like influenza and COVID-19, thus calling for effective prevention and inactivation strategies. Here, we develop a diatomic iron nanozyme with lipoxidase-like (LOX-like) activity for the inactivation of enveloped virus. The diatomic iron sites can destruct the viral envelope via lipid peroxidation, thus displaying non-specific virucidal property.

Theoretical prediction of valley spin splitting in two-dimensional Janus MSiGeZ (M = Cr and W; Z = N, P, and As).

With the exploration of valleytronic materials in MAZ structures, larger valley spin splitting has become a hot topic of research. Based on first-principles calculations, we predicted six valleytronic 2D (two-dimensional) Janus MSiGeZ (M = Cr and W; Z = N, P, and As) materials. The valley spin splitting value of WSiGeZ (Z = N, P, and As) can reach more than 400 meV, which is favorable for the practical application of valleytronics.

Porous Organic Polymers-Supported Zeigler-Natta Catalysts for Preparing Highly Isotactic Polypropylene with Broad Molecular Weight Distribution.

Porous organic polymers (POPs) have attracted much attention in numerous areas, including catalysis, adsorption and separation. Herein, POP supported Ziegler-Natta catalysts were designed for preparation of isotactic polypropylene (iPP). The POPs-based Ziegler-Natta catalysts exhibited the characteristic of broad molecular weight distribution (MWD > 11) with or without adding an extra internal electron donor.

Growth and Optical Properties of Large-Sized NaVO(IO)(HO) Crystals for Second-Harmonic Generation Applications.

Large-sized crystals of the quaternary iodate NaVO(IO)(HO) (NVIO) with centimeter-scale dimensions (23 mm × 18 mm × 6 mm as a representative) have been successfully grown by the top-seeded hydrothermal method. Linear optical properties have been measured, including the optical transmission spectrum and refractive index. The NVIO crystal possesses an optical window with high transmittance (above 80%) over the range of 500-1410 nm and exhibits strong optical anisotropy with large birefringence Δ ( - ) of 0.

Three Gd-based magnetic refrigerant materials with high magnetic entropy: From di-nuclearity to hexa-nuclearity to octa-nuclearity.

Magnetocaloric effect (MCE) is one of the most promising features of molecular-based magnetic materials. We reported three Gd-based magnetic refrigerant materials, namely, Gd(L)(NO)(HO)‧CHCN‧HO (, HL = ()--[(1)-(2-hydroxy-3-methphenyl)methylidene]pyrazine-2-carbohydrazonic acid), {Gd(L)(CO)(CHOH)(HO)Cl}Cl‧4CHCN (), and Gd(L)(CO)(HO)‧2HO (3). Complex contains two Gd ions linked by two : : : : -L ligands, which are seven-coordinated in a capped trigonal prism, and complex possesses six Gd ions, contributing to a triangular prism configuration.

Simplified Transfer Learning for Chest Radiography Models Using Less Data.

Background Developing deep learning models for radiology requires large data sets and substantial computational resources. Data set size limitations can be further exacerbated by distribution shifts, such as rapid changes in patient populations and standard of care during the COVID-19 pandemic. A common partial mitigation is transfer learning by pretraining a "generic network" on a large nonmedical data set and then fine-tuning on a task-specific radiology data set.

Week 96 extension results of a Phase 3 study evaluating long-acting cabotegravir with rilpivirine for HIV-1 treatment.

Background: ATLAS (NCT02951052), a phase 3, multicenter, open-label study, demonstrated that switching to injectable cabotegravir (CAB) with rilpivirine (RPV) long-acting dosed every 4 weeks was noninferior at week (W) 48 to continuing three-drug daily oral current antiretroviral therapy (CAR). Results from the W 96 analysis are presented.

Methods And Design: Participants completing W 52 of ATLAS were given the option to withdraw, transition to ATLAS-2M (NCT03299049), or enter an Extension Phase to continue long-acting therapy (Long-acting arm) or switch from CAR to long-acting therapy (Switch arm).

VEGFR-1/Flt-1 inhibition increases angiogenesis and improves muscle function in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy is characterized by structural degeneration of muscle, which is exacerbated by localized functional ischemia due to loss of nitric oxide synthase-induced vasodilation. Treatment strategies aimed at increasing vascular perfusion have been proposed. Toward this end, we have developed monoclonal antibodies (mAbs) that bind to the vascular endothelial growth factor (VEGF) receptor VEGFR-1 (Flt-1) and its soluble splice variant isoform (sFlt-1) leading to increased levels of free VEGF and proangiogenic signaling.

Small Molecule Inhibition of CPS1 Activity through an Allosteric Pocket.

Carbamoyl phosphate synthetase 1 (CPS1) catalyzes the first step in the ammonia-detoxifying urea cycle, converting ammonia to carbamoyl phosphate under physiologic conditions. In cancer, CPS1 overexpression supports pyrimidine synthesis to promote tumor growth in some cancer types, while in others CPS1 activity prevents the buildup of toxic levels of intratumoral ammonia to allow for sustained tumor growth. Targeted CPS1 inhibitors may, therefore, provide a therapeutic benefit for cancer patients with tumors overexpressing CPS1.

Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing.

Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that cf-mRNA is enriched in transcripts derived from the bone marrow compared to circulating cells.

Draft genome sequence of a multidrug-resistant bla-producing Acinetobacter baumannii L13 isolated from Tarim River sample in China.

Objectives: Acinetobacter baumannii (A. baumannii) is the world's most significant opportunistic pathogen that causes nosocomial infections; there is widespread health concern due to its ability to acquire multidrug resistance. This study reports a new variety of A.

Anti-Deinagkistrodon acutus venom properties of ethanolic root extract from Cynanchum paniculatum (Bunge) kitag and its GC-MS analysis.

Ethnopharmacological Relevance: Cynanchum paniculatum (Bunge) Kitag known as a popular Chinese herbal medicine has been used for a long time to treat a wide variety of diseases including snakebites. However, there is scarce information on the antiophidian potential of this plant.

Aim Of The Study: The purpose of this work was to evaluate the inhibition effects of the ethanol extract of C.

Preparation of Ultrahigh Molecular Weight Polyethylene/Graphene Nanocomposite In situ Polymerization via Spherical and Sandwich Structure Graphene/Sio Support.

Reduced graphene oxide/SiO (RGO/SiO) serving as a novel spherical support for Ziegler-Natta (Z-N) catalyst is reported. The surface and interior of the support has a porous architecture formed by RGO/SiO sandwich structure. The sandwich structure is like a brick wall coated with a graphene layer of concreted as skeleton which could withstand external pressures and endow the structure with higher support stabilities.

Characterization of Degree of Intestinal Fibrosis in Patients with Crohn Disease by Using Magnetization Transfer MR Imaging.

Purpose To evaluate the role of magnetization transfer (MT) magnetic resonance (MR) imaging for the characterization of intestinal fibrosis compared with contrast material-enhanced and diffusion-weighted MR imaging and its capability for differentiating fibrotic from inflammatory strictures in humans with Crohn disease (CD) by using surgical histopathologic analysis as the reference standard. Materials and Methods Institutional review board approval and informed consent were obtained for this prospective study. Abdominal MT imaging, contrast-enhanced imaging, and diffusion-weighted imaging of 31 consecutive patients with CD were analyzed before elective surgery.

Hyperbaric Oxygen Reduces Infarction Volume and Hemorrhagic Transformation Through ATP/NAD/Sirt1 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats.

Background And Purpose: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO).

Methods: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion.

Bioactive Isoprenoid-Derived Natural Products from a Dongsha Atoll Soft Coral Sinularia erecta.

Four new isoprenoids, including two norcembranoids sinulerectols A and B (1 and 2), a cembranoid sinulerectol C (3), and a degraded cembranoid sinulerectadione (4), along with three known isoprenoids, an unnamed norcembrene (5), sinularectin (6), and ineleganolide (7), and a known nitrogen-containing compound (Z)-N-[2-(4-hydroxyphenyl)ethyl]-3-methyldodec-2-enamide (8), were isolated from an extract of the marine soft coral Sinularia erecta. The structure of sinularectin (6) was revised, too. Compounds 3, 4, and 8 exhibited inhibitory activity against the proliferation of a limited panel of cancer cell lines, whereas 1, 2, and 8 displayed potent anti-inflammatory activity in fMLP/CB-stimulated human neutrophils.

Effect of Performance Deficiencies on Graduation and Board Certification Rates: A 10-yr Multicenter Study of Anesthesiology Residents.

Background: This multicenter, retrospective study was conducted to determine how resident performance deficiencies affect graduation and board certification.

Methods: Primary documents pertaining to resident performance were examined over a 10-yr period at four academic anesthesiology residencies. Residents entering training between 2000 and 2009 were included, with follow-up through February 2016.

(Z)-N-[(Z)-3-(2,5-Di-methyl-phenyl-imino)-butan-2-yl-idene]-2,5-di-methyl-aniline.

The asymmetric unit of the title compound, C20H24N2, contains one half-mol-ecule, with the single C-C bond of the 1,4-di-aza-butadiene fragment situated on a centre of symmetry. The benzene rings are inclined to the 1,4-di-aza-butadiene mean plane by 59.5 (1)°.

Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation.

Tau protein was scanned for highly amyloidogenic sequences in amphiphilic motifs (X)(n)Z, Z(X)(n)Z (n ≥ 2), or (XZ)(n) (n ≥ 2), where X is a hydrophobic residue and Z is a charged or polar residue. N-Acetyl peptides homologous to these sequences were used to study aggregation. Transmission electron microscopy (TEM) showed seven peptides, in addition to well-known primary nucleating sequences Ac(275)VQIINK (AcPHF6*) and Ac(306)VQIVYK (AcPHF6), formed fibers, tubes, ribbons, or rolled sheets.