Genome-edited powdery mildew resistance in wheat without growth penalties.

Disruption of susceptibility (S) genes in crops is an attractive breeding strategy for conferring disease resistance1,2. However, S genes are implicated in many essential biological functions and deletion of these genes typically results in undesired pleiotropic effects1. Loss-of-function mutations in one such S gene, Mildew resistance locus O (MLO), confers durable and broad-spectrum resistance to powdery mildew in various plant species2,3. However, mlo-associated resistance is also accompanied by growth penalties and yield losses3,4, thereby limiting its widespread use in agriculture. Here we describe Tamlo-R32, a mutant with a 304-kilobase pair targeted deletion in the MLO-B1 locus of wheat that retains crop growth and yields while conferring robust powdery mildew resistance. We show that this deletion results in an altered local chromatin landscape, leading to the ectopic activation of Tonoplast monosaccharide transporter 3 (TaTMT3B), and that this activation alleviates growth and yield penalties associated with MLO disruption. Notably, the function of TMT3 is conserved in other plant species such as Arabidopsis thaliana. Moreover, precision genome editing facilitates the rapid introduction of this mlo resistance allele (Tamlo-R32) into elite wheat varieties. This work demonstrates the ability to stack genetic changes to rescue growth defects caused by recessive alleles, which is critical for developing high-yielding crop varieties with robust and durable disease resistance.

Rationally Designed APOBEC3B Cytosine Base Editors with Improved Specificity.

Cytosine base editors (CBEs) generate C-to-T nucleotide substitutions in genomic target sites without inducing double-strand breaks. However, CBEs such as BE3 can cause genome-wide off-target changes via sgRNA-independent DNA deamination. By leveraging the orthogonal R-loops generated by SaCas9 nickase to mimic actively transcribed genomic loci that are more susceptible to cytidine deaminase, we set up a high-throughput assay for assessing sgRNA-independent off-target effects of CBEs in rice protoplasts. The reliability of this assay was confirmed by the whole-genome sequencing (WGS) of 10 base editors in regenerated rice plants. The R-loop assay was used to screen a series of rationally designed A3Bctd-BE3 variants for improved specificity. We obtained 2 efficient CBE variants, A3Bctd-VHM-BE3 and A3Bctd-KKR-BE3, and the WGS analysis revealed that these new CBEs eliminated sgRNA-independent DNA off-target edits in rice plants. Moreover, these 2 base editor variants were more precise at their target sites by producing fewer multiple C edits.

Multifunctional Iron Selenate Sheath of Fe-Based Anode Achieving High-Rate Capacity-Durability Combination of Aqueous Hybrid Energy Storage Devices.

The introduction of battery-type cathode has been commonly considered a preferred approach to boost the energy density of aqueous hybrid energy storage devices (AHESDs) in alkalic systems, but AHESDs with both high energy density and power density are rare due to the great challenge in designing battery-type anode materials with high rate and durability comparable to capacitive-type carbon anodes. In this paper, a well-hydrated iron selenate (FeSeO) sheath is constructed around FeOOH nanorods by a facile electrochemical activation, demonstrating the unique multifunction in fasting charge diffusion, promoting the dissociation of H2O, and inhibiting the irreversible phase transition of FeOOH to inert γ-Fe2O3, which endow the hydrated sheath coated Fe-based anodes with an impressive rate capability and superior durability. Thanks to the comprehensive performance of this Fe-based anode, the assembled AHESD delivered a high energy density of 117 Wh kg-1 with the extraordinary durability of almost 100% capacity retention after 40 000 cycles. Even at an ultrahigh power density of 27 000 W kg-1, an impressive energy density of 65 Wh kg-1 can be achieved, which rivals previously reported energy-storage devices.

Endometrium procurement and transplantation restores fertility in rats.

RESEARCH QUESTION: Can rat endometrium be successfully procured and transplanted, and can a similar method be used to procure human endometrium? DESIGN: Rat endometrium was procured using an endometrium stripping method and transplanted into female Sprague-Dawley rats. Macroscopic and histological changes, endometrial receptivity-related protein concentrations and fertility were assessed. Additionally, a preliminary experiment was conducted to procure human endometrium using a similar method. RESULTS: Endometrium was successfully procured from both rats and humans, which contained intact endometrium and parts of the adjacent inner annulus myometrium. Endometrium auto-transplantation was conducted in rats and the procedure lasted a total of 41.3 ± 5.7 min with a mean blood loss of 0.09 ± 0.04 g. The transplanted endometrium survived well, but a fibrotic zone formed between the transplant and recipient tissue. Compared with sham rats, those with endometrium transplantation had similar endometrial thickness and endometrial gland numbers but reduced vascular density at 8 weeks after surgery. Endometrium transplantation also retained expression of the endometrial receptivity-related proteins leukaemia inhibitory factor and vascular endothelial growth factor. In contrast to non-pregnancy in the stripped horn, a mean of 5.0 ± 2.7 fetuses developed in the transplanted horn, and full-term live fetuses were conceived in the horns with transplanted endometrium. CONCLUSIONS: Endometrium procurement by stripping method can obtain an intact and functional endometrium, and endometrium transplantation can reconstruct the uterine cavity and restore fertility in rats.

Achieving high-capacity aqueous supercapacitors via anion-doped construction of dual redox centers in NixCo1-xSeO3.

In asymmetric supercapacitors, transition metal selenates are promising electrodes, but their capacity are limited by a single redox center. To further enhance the performance of transition metal selenates, NixCo1-xSeO3 (NCSeO) doped with N and Cl was prepared on nickel-plated carbon cloth (NCSeO-NCl-NiCC). During electrochemical reactions, NCSeO can be converted to M(OH)2 (M = Ni/Co) and OH- is replaced by N and Cl. Two redox centers, M(OH)2/MOOH and M(OH)xN2-x/NO3-, are formed during charging and discharging, which is attributed to the increased capacity of the NCSeO-NCl-NiCC electrode. On NCSeO, the substitution of Cl facilitates the regulation of the electronic structure and enhances the stability of N-doping. The optimised electrode exhibits a high capacity of 417 mA h g-1 at 1 A g-1 and an impressive rate capability of 235 mA h g-1 at 50 A g-1. Asymmetric supercapacitors with this design have an ultra-high energy density of 73.6 W h kg-1, as well as an excellent rate and cycling performance with a capacitance retention of 97.8% after 20 000 cycles at a current density of 20 A g-1.

Clinical incidence and relevance of incomplete endothelialization in atrial fibrillation patients with Left Atrial Appendage Closure.

BACKGROUND: The objective of this study is to investigate the incidence, potential risk factors, and clinical outcomes of incomplete device endothelialization (IDE) in atrial fibrillation (AF) patients undergoing Watchman left atrial appendage closure (LAAC). METHODS: In this study, 68 AF patients who underwent successful implantation of the Watchman device without peri-device leak (PDL) during follow-up were included. The endothelialization status was assessed using Transesophageal echocardiography (TEE) and LAA computed tomography angiography (CTA) at 6 weeks and 6 months post-implantation. Adverse cerebro-cardiac events were documented at one-year follow-up. Baseline characteristics, including age, device sizes, and clinical indicators, were analyzed as potential predictors for IDE. RESULTS: IDE was observed in 70.6% and 67.6% of patients at 6 weeks and 6 months after implantation, respectively. Higher levels of high-density lipoprotein cholesterol (HDL-C) [odds ratio (OR): 15.109, 95% confidence interval (CI): 1.637-139.478, p = 0.017 and OR: 11.015, 95% CI: 1.365-88.896, p = 0.024] and lower aspartate aminotransferase (AST) (OR 0.924, 95% CI: 0.865-0.986, p = 0.017 and OR: 0.930, 95% CI: 0.874-0.990, p = 0.023) at baseline were found to be significantly associated with IDE at 6 weeks and 6 months, respectively, although no significant difference in adverse cerebro-cardiac events was noted between incomplete and complete DE groups during 1-year follow-up CONCLUSIONS: IDE is found to be a prevalent occurrence in humans following LAAC. Elevated HDL-C and reduced AST levels are shown to be linked to an increased risk of IDE after LAAC.

Expressions of Type I-III Interferons in Sjögren's Syndrome and Non-Sjögren's Dry Eye.

INTRODUCTION: Systemic implications create a critical need for identification of dry eye patients with Sjögren syndrome (SS). Herein, we aimed to determine expressions of type I-III interferons (IFNs) in dry eye patients with or without underlying SS and their differential diagnosis. METHODS: A prospective, observational, case-control study was performed on 140 dry eye patients among which 78 patients were diagnosed with SS. Clinical evaluations included ELISA detections of serum type I IFN (IFN-α and IFN-ß, type II IFN (IFN-γ), and type III IFN (IFN-λ1/IL-29, IFN-λ2/IL-28, and IFN-λ3/IL-28B), as well as reporter cell assay for serum type I IFN activity. RESULTS: The serum levels of IFN-α and IFN-ß were notably higher in dry eye patients with SS than those without underlying SS (p < 0.0001). The functional assay for serum type I IFN activity showed the mean summed scores in dry eye patients with SS were remarkably increased compared to those without underlying SS (p < 0.0001). The serum levels of IFN-γ and IFN-λ1/IL-29 seemed higher in dry eye patients with SS than those without underlying SS (p < 0.0001). The serum levels of type I IFN (IFN-α combined with IFN-ß), type II IFN (IFN-γ level), and type III IFN (IFN-λ1/IL-29) used as a test to predict underlying SS among dry eye patients produced an area under the curve of 0.86, 0.73, and 0.94, respectively. CONCLUSION: Serum levels of type I-III IFNs, especially IFN-α, IFN-ß, and IFN-λ1/IL-29, may serve as a useful biomarker for identification of SS dry eye from non-SS dry eye.

Single-cell profiling of ineffective erythropoiesis in a mouse model of ß-thalassaemia intermedia.

Beta-thalassaemia is an inherited haemoglobin disorder characterised by ineffective erythropoiesis (IE). The detailed pathogenesis of IE remains unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to examine IE in Th3/+ ß-thalassaemic mice. The results showed that the erythroid group was remarkably expanded, and genes involved in biological processes such as iron metabolism, haeme synthesis, protein folding, and response to heat were significantly upregulated from erythroid progenitors to reticulocytes in ß-thalassaemic mice. In particular, we identified a unique cell population close to reticulocytes, named ThReticulocytes, characterised by a high level of heat shock protein 70 (Hsp70) expression and dysregulation of iron metabolism and haeme synthesis signalling. Treatment of ß-thalassaemic mice with the haeme oxygenase inhibitor tin-mesoporphyrin effectively improved the iron disorder and IE, and the ThReticulocyte population and Hsp70 expression were significantly suppressed. This study revealed in detail the progression of IE at the single-cell level and possibly provided clues to find therapeutic targets in thalassaemia.

Engineering of Siloxanes for Stabilizing Silicon Anode Materials.

Silicon (Si) is considered the most promising anode material for the next generation of lithium-ion batteries (LIBs) because of its high theoretical specific capacity and abundant reserves. However, the volume expansion of silicon in the cycling process causes the destruction of the electrode structure and irreversible capacity loss. As a result, the commercial application of silicon materials is greatly hindered. In recent years, siloxane-based organosilicon materials have been widely used in silicon anode of LIBs because of their unique structure and physical and chemical properties, and have shown excellent electrochemical properties. The comprehensive achievement of siloxanes in silicon-based LIBs can be understood better through a systematic summary, which is necessary to guide the design of electrodes and achieve better electrochemical performance. This paper systematically introduces the unique advantages of siloxane materials in electrode, surface/interface modification, binder, and electrolyte. The challenges and future directions for siloxane materials are presented to enhance their performance and expand their application in silicon-based LIBs.

General Spatial Confinement Recrystallization Method for Rapid Preparation of Thickness-Controllable and Uniform Organic Semiconductor Single Crystals.

Organic semiconductor single crystals (OSSCs) are ideal materials for studying the intrinsic properties of organic semiconductors (OSCs) and constructing high-performance organic field-effect transistors (OFETs). However, there is no general method to rapidly prepare thickness-controllable and uniform single crystals for various OSCs. Here, inspired by the recrystallization (a spontaneous morphological instability phenomenon) of polycrystalline films, a spatial confinement recrystallization (SCR) method is developed to rapidly (even at several second timescales) grow thickness-controllable and uniform OSSCs in a well-controlled way by applying longitudinal pressure to tailor the growth direction of grains in OSCs polycrystalline films. The relationship between growth parameters including the growth time, temperature, longitudinal pressure, and thickness is comprehensively investigated. Remarkably, this method is applicable for various OSCs including insoluble and soluble small molecules and polymers, and can realize the high-quality crystal array growth. The corresponding 50 dinaphtho[2,3-b:2″,3″-f]thieno[3,2-b]thiophene (DNTT) single crystals coplanar OFETs prepared by the same batch have the mobility of 4.1 ± 0.4 cm2 V-1 s-1 , showing excellent uniformity. The overall performance of the method is superior to the reported methods in term of growth rate, generality, thickness controllability, and uniformity, indicating its broad application prospects in organic electronic and optoelectronic devices.