Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes.

Lysosomes require an acidic lumen between pH 4.5 and 5.0 for effective digestion of macromolecules. This pH optimum is maintained by proton influx produced by the V-ATPase and efflux through an unidentified "H+ leak" pathway. Here we show that TMEM175, a genetic risk factor for Parkinson's disease (PD), mediates the lysosomal H+ leak by acting as a proton-activated, proton-selective channel on the lysosomal membrane (LyPAP). Acidification beyond the normal range potently activated LyPAP to terminate further acidification of lysosomes. An endogenous polyunsaturated fatty acid and synthetic agonists also activated TMEM175 to trigger lysosomal proton release. TMEM175 deficiency caused lysosomal over-acidification, impaired proteolytic activity, and facilitated α-synuclein aggregation in vivo. Mutational and pH normalization analyses indicated that the channel's H+ conductance is essential for normal lysosome function. Thus, modulation of LyPAP by cellular cues may dynamically tune the pH optima of endosomes and lysosomes to regulate lysosomal degradation and PD pathology.

High-dimensional generalized median adaptive lasso with application to omics data.

Recently, there has been a growing interest in variable selection for causal inference within the context of high-dimensional data. However, when the outcome exhibits a skewed distribution, ensuring the accuracy of variable selection and causal effect estimation might be challenging. Here, we introduce the generalized median adaptive lasso (GMAL) for covariate selection to achieve an accurate estimation of causal effect even when the outcome follows skewed distributions. A distinctive feature of our proposed method is that we utilize a linear median regression model for constructing penalty weights, thereby maintaining the accuracy of variable selection and causal effect estimation even when the outcome presents extremely skewed distributions. Simulation results showed that our proposed method performs comparably to existing methods in variable selection when the outcome follows a symmetric distribution. Besides, the proposed method exhibited obvious superiority over the existing methods when the outcome follows a skewed distribution. Meanwhile, our proposed method consistently outperformed the existing methods in causal estimation, as indicated by smaller root-mean-square error. We also utilized the GMAL method on a deoxyribonucleic acid methylation dataset from the Alzheimer's disease (AD) neuroimaging initiative database to investigate the association between cerebrospinal fluid tau protein levels and the severity of AD.

Significantly Enhanced Energy-Saving H2 Production Coupled with Urea Oxidation by Low- and Non-Pt Anchored on NiS-Based Conductive Nanofibers.

Rational designing electrocatalysts is of great significance for realizing high-efficiency H2 production in the water splitting process. Generally, reducing the usage of precious metals and developing low-potential nucleophiles oxidation reaction to replace anodic oxygen evolution reaction (OER) are efficient strategies to promote H2 generation. Here, NiS-coated nickel-carbon nanofibers (NiS@Ni-CNFs) are prepared for low-content Pt deposition (Pt-NiS@Ni-CNFs) to attain the alkaline HER catalyst. Due to the reconfiguration of NiS phase and synergistic effect between Pt and nickel sulfides, the Pt-NiS@Ni-CNFs catalyst shows a high mass activity of 2.74-fold of benchmark Pt/C sample. In addition, the NiS@Ni-CNFs catalyst performs a superior urea oxidation reaction (UOR) activity with the potential of 1.366 V versus reversible hydrogen electrode (RHE) at 10 mA cm-2 , which demonstrates the great potential in the replacement of OER. Thus, a urea-assisted water splitting electrolyzer of Pt-NiS@Ni-CNFs (cathode)||NiS@Ni-CNFs (anode) is constructed to exhibit small voltages of 1.44 and 1.65 V to reach 10 and 100 mA cm-2 , which is much lower than its overall water splitting process, and presents a 6.5-fold hydrogen production rate enhancement. This work offers great opportunity to design new catalysts toward urea-assisted water splitting with significantly promoted hydrogen productivity and reduced energy consumption.

Rationally Construction of Mn-Doped RuO2 Nanofibers for High-Activity and Stable Alkaline Ampere-Level Current Density Overall Water Splitting.

Nowadays, highly active and stable alkaline bifunctional electrocatalysts toward water electrolysis that can work at high current density (≥1000 mA cm-2) are urgently needed. Herein, Mn-doped RuO2 (MnxRu1-xO2) nanofibers (NFs) are constructed to achieve this object, presenting wonderful hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performances with the overpotentials of only 269 and 461 mV at 1 A cm-2 in 1 m KOH solution, and remarkably stability under industrial demand with 1 A cm-2, significantly better than the benchmark Pt/C and commercial RuO2 electrocatalysts, respectively. More importantly, the assembled Mn0.05Ru0.95O2 NFs||Mn0.05Ru0.95O2 NFs electrolyzer toward overall water splitting reaches the current density of 10 mA cm-2 with a cell voltage of 1.52 V and also delivers an outstanding stability over 150 h of continuous operation, far surpassing commercial Pt/C||commercial RuO2, RuO2 NFs||RuO2 NFs and most previously reported exceptional electrolyzers. Theoretical calculations indicate that Mn-doping into RuO2 can significantly optimize the electronic structure and weaken the strength of O─H bond to achieve the near-zero hydrogen adsorption free energy (ΔGH*) value for HER, and can also effectively weaken the adsorption strength of intermediate O* at the relevant sites, achieving the higher OER catalytic activity, since the overlapping center of p-d orbitals is closer to the Fermi level.

Magnesium Ions Promote the Induction of Immunosuppressive Bone Microenvironment and Bone Repair through HIF-1α-TGF-ß Axis in Dendritic Cells.

The effect of immunoinflammation on bone repair during the recovery process of bone defects needs to be further explored. It is reported that Mg2+ can promote bone repair with immunoregulatory effect, but the underlying mechanism on adaptive immunity is still unclear. Here, by using chitosan and hyaluronic acid-coated Mg2+ (CSHA-Mg) in bone-deficient mice, it is shown that Mg2+ can inhibit the activation of CD4+ T cells and increase regulatory T cell formation by inducing immunosuppressive dendritic cells (imDCs). Mechanistically, Mg2+ initiates the activation of the MAPK signaling pathway through TRPM7 channels on DCs. This process subsequently induces the downstream HIF-1α expression, a transcription factor that amplifies TGF-ß production and inhibits the effective T cell function. In vivo, knock-out of HIF-1α in DCs or using a HIF-1α inhibitor PX-478 reverses inhibition of bone inflammation and repair promotion upon Mg2+-treatment. Moreover, roxadustat, which stabilizes HIF-1α protein expression, can significantly promote immunosuppression and bone repair in synergism with CSHA-Mg. Thus, the findings identify a key mechanism for DCs and its HIF-1α-TGF-ß axis in the induction of immunosuppressive bone microenvironment, providing potential targets for bone regeneration.

Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Photoperiod-responsive changes in chromatin accessibility in phloem companion and epidermis cells of Arabidopsis leaves.

Photoperiod plays a key role in controlling the phase transition from vegetative to reproductive growth in flowering plants. Leaves are the major organs perceiving day-length signals, but how specific leaf cell types respond to photoperiod remains unknown. We integrated photoperiod-responsive chromatin accessibility and transcriptome data in leaf epidermis and vascular companion cells of Arabidopsis thaliana by combining isolation of nuclei tagged in specific cell/tissue types with assay for transposase-accessible chromatin using sequencing and RNA-sequencing. Despite a large overlap, vasculature and epidermis cells responded differently. Long-day predominantly induced accessible chromatin regions (ACRs); in the vasculature, more ACRs were induced and these were located at more distal gene regions, compared with the epidermis. Vascular ACRs induced by long days were highly enriched in binding sites for flowering-related transcription factors. Among the highly ranked genes (based on chromatin and expression signatures in the vasculature), we identified TREHALOSE-PHOSPHATASE/SYNTHASE 9 (TPS9) as a flowering activator, as shown by the late flowering phenotypes of T-DNA insertion mutants and transgenic lines with phloem-specific knockdown of TPS9. Our cell-type-specific analysis sheds light on how the long-day photoperiod stimulus impacts chromatin accessibility in a tissue-specific manner to regulate plant development.

Synthesis and Characterization of a Novel PET Tracer for Noninvasive Evaluation of FGL1 Status in Tumors.

Fibrinogen-like protein 1 (FGL1) is a potential novel immune checkpoint target for malignant tumor diagnosis and therapy. Accurate detection of FGL1 levels in tumors via noninvasive PET imaging might be beneficial for managing the disease. To achieve this, multiple FGL1-targeting peptides (FGLP) were designed, and a promising candidate, 68Ga-NOTA-FGLP2, was identified through a high-throughput screening approach using microPET imaging of 68Ga-labeled peptides. Subsequent in vitro cell experiments showed that uptake values of 68Ga-NOTA-FGLP2 in FGL1 positive Huh7 tumor cells were significantly higher than those in FGL1 negative U87 MG tumor cells. Further microPET imaging showed that the Huh7 xenografts were clearly visualized with a favorable contrast. ROI analysis showed that the uptake values of the tracer in Huh7 xenografts were 2.63 ± 0.07% ID/g at 30 min p.i.. After treatment with an excess of unlabeled FGLP2, the tumor uptake significantly decreased to 0.54 ± 0.05% ID/g at 30 min p.i.. Moreover, the uptake in U87 MG xenografts was 0.44 ± 0.06% ID/g at the same time point. The tracer was excreted mainly through the renal system. 18F-FDG PET imaging was also performed in mice bearing Huh7 and U87 MG xenografts, respectively. However, there was no significant difference in the uptake between the tumors with different FGL1 expressions. Preclinical data indicated that 68Ga-NOTA-FGLP2 might be a suitable radiotracer for in vivo noninvasive visualization of tumors with abundant expression of FGL1. Further investigation of 68Ga-NOTA-FGLP2 for tumor diagnosis and therapy is undergoing.

Small extracellular vesicles' enrichment from biological fluids using an acoustic trap.

Small extracellular vesicles (sEVs), a form of extracellular vesicles, are lipid bilayered structures released by all cells. Large-scale studies on sEVs from clinical samples are necessary, but a major obstacle is the lack of rapid, reproducible, efficient, and low-cost methods to enrich sEVs. Acoustic microfluidics have the advantage of being label-free and biocompatible, which have been reported to successfully enrich sEVs. In this paper, we present a highly efficient acoustic microfluidic trap that can offer low and large volume compatible ways of enriching sEVs from biological fluids by flexible structure design. It uses the idea of pre-loading larger seed particles in the acoustic trap to enable sub-micron particle capturing. The microfluidic chip is actuated using a piezoelectric plate transducer attached to a silicon-glass bonding plate with circular cavities. Each cavity works as a resonant unit, excited at the frequency of both the half wave resonance in the main plane and inverted quarter wave resonance in the depth direction, which has the ability to strongly trap seed particles at the center, thereby improving the subsequent nanoparticle capture efficiency. Mean trapping efficiencies of 35.62% and 64.27% were obtained using 60 nm and 100 nm nanobeads, respectively. By the use of this technology, we have successfully enriched sEVs from cell culture conditioned media and blood plasma at a flow rate of 10 µL min-1. The isolated sEV subpopulations are characterized by NTA and TEM, and their protein cargo is determined by WB. This acoustic trapping chip provides a rapid and robust method to enrich sEVs from biofluids with high reproducibility and sufficient quantities. Therefore, it can serve as a new tool for biological and clinical research such as cancer diagnosis and drug delivery.

Author Correction: Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.

In the originally published version of this Letter, the authors Arthur F. Kluge, Michael A. Patane and Ce Wang were inadvertently omitted from the author list. Their affiliations are: I-to-D, Inc., PO Box 6177, Lincoln, Massachusetts 01773, USA (A.F.K.); Mitobridge, Inc. 1030 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (M.A.P.); and China Novartis Institutes for BioMedical Research, No. 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong District, Shanghai 201203, China (C.W.). These authors contributed to the interpretation of results and design of compounds. In addition, author 'Edward A. Kesicki' was misspelled as 'Ed Kesicki'. These errors have been corrected online.

Effects of eutrophication on the horizontal transfer of antibiotic resistance genes in microalgal-bacterial symbiotic systems.

Overloading of nutrients such as nitrogen causes eutrophication of freshwater bodies. The spread of antibiotic resistance genes (ARGs) poses a threat to ecosystems. However, studies on the enrichment and spread of ARGs from increased nitrogen loading in algal-bacterial symbiotic systems are limited. In this study, the transfer of extracellular kanamycin resistance (KR) genes from large (RP4) small (pEASY-T1) plasmids into the intracellular and extracellular DNA (iDNA, eDNA) of the inter-algal environment of Chlorella pyrenoidosa was investigated, along with the community structure of free-living (FL) and particle-attached (PA) bacteria under different nitrogen source concentrations (0-2.5 g/L KNO3). The results showed that KR gene abundance in the eDNA adsorbed on solid particles (D-eDNA) increased initially and then decreased with increasing nitrogen concentration, while the opposite was true for the rest of the free eDNA (E-eDNA). Medium nitrogen concentrations promoted the transfer of extracellular KR genes into the iDNA attached to algal microorganisms (A-iDNA), eDNA attached to algae (B-eDNA), and the iDNA of free microorganisms (C-iDNA); high nitrogen contributed to the transfer of KR genes into C-iDNA. The highest percentage of KR genes was found in B-eDNA with RP4 plasmid treatment (66.2%) and in C-iDNA with pEASY-T1 plasmid treatment (86.88%). In addition, dissolved oxygen (DO) significantly affected the bacterial PA and FL community compositions. Nephelometric turbidity units (NTU) reflected the abundance of ARGs in algae. Proteobacteria, Cyanobacteria, Bacteroidota, and Actinobacteriota were the main potential hosts of ARGs. These findings provide new insights into the distribution and dispersal of ARGs in the phytoplankton inter-algal environment.

Correlation between plasma lycopene levels in patients with laryngeal carcinoma and postoperative adverse complications of chemoradiotherapy and nutritional risks.

OBJECTIVE: In this study, we analyzed the correlation between the preoperative plasma lycopene levels, postoperative adverse complications of chemoradiotherapy, and nutritional risk scores in patients with laryngeal carcinoma. METHODS: A total of 114 patients with laryngeal carcinoma and 114 healthy respondents were enrolled in this study. The patients with laryngeal carcinoma were divided into two groups: 62 patients with laryngeal carcinoma, with an NRS2002 score higher than 3 points and whose diet contained lycopene, were enrolled in the observation group, and 52 patients with laryngeal carcinoma during the corresponding time period, whose diet did not contain lycopene, were enrolled in the reference group. The immune indexes (CD4 + , CD8 + , IGA, IGM, IGG), nutritional indexes (albumin, prealbumin, transferrin), and postoperative adverse complications of chemo-radiotherapy in the two groups were recorded. RESULTS: The lycopene levels were lower in patients with advanced tumor stage (III and IV). The diagnosis threshold of the plasma lycopene level for laryngeal carcinoma was 0.503 µmol/L. The area under the curve for plasma lycopene levels in cancer diagnosis was 0.96, with a clinical specificity of 0.943 and a sensitivity of 0.859. There was a significant negative correlation between the plasma lycopene levels and Nutrition Risk Screening (NRS) 2002 score (R2 = - 0.523, P < 0.001), which was related to the increase in NRS-2002 scores and nutritional hazards in patients with laryngeal carcinoma. The observation group showed a significant increase in nutritional and immune indices, as compared to the reference group, as well as a lower incidence of severe and serious adverse reactions to chemo-radiotherapy. Lycopene supplementation, tumor stage, NRS-2002 scores, nutritional and immune indices were all significant predictors of postoperative severe and serious adverse complications of chemoradiotherapy. CONCLUSION: Progression of laryngeal carcinoma and severity of the side effects of the adverse complications of chemo-radiotherapy are related to the levels of lycopene.

Effect of black wolfberry anthocyanin and maltitol on the gelation and microstructural properties of curdlan/gellan gum hybrid gels.

BACKGROUND: Laboratory scale experiments have shown that curdlan and gellan gum gelled together as curdlan/gellan gum (CG) hybrid gels showed better gel properties than the individual curdlan and gellan gum. In this study, CG and black wolfberry anthocyanin (BWA), CG and maltitol (ML) hybrid gels were constructed using CG hybrid gel as matrix. The effects of BWA or ML on the gel properties and microstructure of CG hybrid gels were investigated and a confectionery gel was developed. RESULTS: The presence of BWA increased the storage modulus (G') value of CG at 0.1 Hz, whereas ML had little effect on the G' value of CG. The addition of BWA (5 g L-1 ) and ML (0.3 mol L-1 ) increased the melting and gelling temperatures of CG hybrid gels to 42.4 °C and 34.1 °C and 44.2 °C and 33.2 °C, respectively. Meanwhile, the relaxation time T22 in CG-ML and CG-BWA hybrid gels was reduced to 91.96 and 410.27 ms, indicating the strong binding between BWA and CG, ML and CG. The hydrogen bond interaction between BWA or ML and CG was confirmed by the shift in the hydroxyl stretching vibration peak. Moreover, the microstructures of CG-ML and CG-BWA hybrid gels were denser than that of CG. In addition, confectionery gel containing CG-BWA-ML has good chewing properties. CONCLUSION: These results indicated that the incorporation of BWA or ML could improve the structure of CG hybrid gels and assign a sustainability potential for the development of confectionery gels based on CG complex. © 2024 Society of Chemical Industry.

Effects of cognitive behavioral and psychological intervention on social adaptation, psychological resilience and level of hope in patients with nasopharyngeal carcinoma in radiotherapy.

Objective: To evaluate the effects of cognitive behavioral and psychological intervention(CBPI) on social adaptation, psychological resilience, and the level of hope in patients with nasopharyngeal carcinoma(NPC) in radiotherapy. Methods: This is application research. Eighty patients undergoing radiotherapy for NPC at Affiliated Hospital of Hebei University from November 20, 2020 to November 15, 2022 were randomized into control and study groups at a 1:1 ratio. While the control group was provided with standard specialized nursing care, the study group was offered CBPI in addition to the exact nursing care. Differences in quality of life, psychological resilience, level of hope, emotional state, and patient satisfaction between the groups were compared and analyzed before and after treatment. Results: After an intervention, significantly improved physical, mental, and social functions and material living conditions were observed in the study group compared with the control group (all p< 0.05). Although both groups scored higher on the selected psychological resilience scale following the intervention, the study group showed better results as compared to control group in adaptability, tenacity, control, and goal orientation (all p< 0.05). While both groups had elevated scores of temporality and future, interconnectedness, and positive readiness and expectancy at the end of the intervention, the improvements were more pronounced in the study group (all p< 0.05). Conclusion: CBPI supports radiotherapy for NPC by improving patients' quality of life, confidence in treatment, the hope of recovery, psychological resilience, anxiety, depression, and patient satisfaction. Therefore, this treatment strategy is worthy of wide application in clinical settings.

A Piezoelectric-Driven Electrochromic/Electrofluorochromic Dual-Modal Display Device.

Electrochromic (EC) reflective displays offer great advantages in delivering information and providing visual data, but are limited in dark environments. Reflective/emissive dual-modal displays capable of electrochemically-induced color and fluorescence change simultaneously are highly desirable, especially possessing rapid response speed as well as long-term durability. Herein, an electroactive fluorescent ionic liquid based on triphenylamine and imidazole (EFIL-TPA) has been synthesized for reflective/emissive dual-modal display. The resultant device exhibits outstanding electrochromic/electrofluorochromic (EC/EFC) performance with low driving voltage (below 1.0 V), fast switching speed (0.57-1.8 s), and remarkable cycling durability (91% retention for 10 000 cycles). A piezoelectric nanogenerator (PENG) driven EC/EFC integrated system is fabricated to harvest energy from human motion and visually drive the color/fluorescence change for human motion indication in both bright and dark environments. This innovative EC/EFC dual-modal display device based on EFIL-TPA supports a huge space for the development of self-powered human motion visualized indication in all-light conditions.

Functional Separator Enabled by Covalent Organic Frameworks for High-Performance Li Metal Batteries.

Uncontrolled ion transport and susceptible SEI films are the key factors that induce lithium dendrite growth, which hinders the development of lithium metal batteries (LMBs). Herein, a TpPa-2SO3 H covalent organic framework (COF) nanosheet adhered cellulose nanofibers (CNF) on the polypropylene separator (COF@PP) is successfully designed as a battery separator to respond to the aforementioned issues. The COF@PP displays dual-functional characteristics with the aligned nanochannels and abundant functional groups of COFs, which can simultaneously modulate ion transport and SEI film components to build robust lithium metal anodes. The Li//COF@PP//Li symmetric cell exhibits stable cycling over 800 h with low ion diffusion activation energy and fast lithium ion transport kinetics, which effectively suppresses the dendrite growth and improves the stability of Li+ plating/stripping. Moreover, The LiFePO4//Li cells with COF@PP separator deliver a high discharge capacity of 109.6 mAh g-1 even at a high current density of 3 C. And it exhibits excellent cycle stability and high capacity retention due to the robust LiF-rich SEI film induced by COFs. This COFs-based dual-functional separator promotes the practical application of lithium metal batteries.

Synergistic Integration of Amorphous Cobalt Phosphide with a Conductive Channel for Highly Efficient Electrocatalytic Nitrate Reduction to Ammonia.

Electrocatalytic nitrate reduction to ammonia (NO3 RR) is regarded as a viable alternative reaction to "Haber Bosch" process. Nevertheless, it remains a major challenge to explore economical and efficient electrocatalysts that deliver high NH3 yield rates and Faraday efficiencies (FE). Here, it demonstrates the fabrication of a 3D core-shell structured Co-carbon nanofibers (CNF)/ZIF-CoP for NO3 RR application. Benefitting from the distinct electron transport property of Co-CNF and desirable mass transfer ability from amorphous CoP framework, the as-prepared Co-CNF/ZIF-CoP exhibits large NH3 FE (96.8 ± 3.4% at -0.1 V vs reversible hydrogen electrode (RHE)) and high yield rate (38.44 ± 0.65 mg cm-2 h-1 at -0.6 V vs RHE), which are better than Co-CNF/ZIF-crystal CoP. Density functional theory (DFT) calculations further reveal that amorphous CoP presents a lower energy barrier in the rate determination step of the protonation of *NO to produce *NOH intermediates compared with crystal CoP, resulting in a superior NO3 RR performance. Eventually, an aqueous galvanic Zn-NO3 - battery is assembled by using Co-CNF/ZIF-CoP as cathode material to achieve efficient production of NH3 whilst simultaneously supplying electrical power. This work offers a reliable strategy to construct amorphous metal phosphide framework on conducting CNF as efficient electrocatalyst and enriches its promising application for NO3 RR.

Simultaneous editing of three homoeologues of TaCIPK14 confers broad-spectrum resistance to stripe rust in wheat.

Wheat stripe rust caused by the fungus Puccinia striiformis f. sp. tritici (Pst) is one of the most destructive wheat diseases resulting in significant losses to wheat production worldwide. The development of disease-resistant varieties is the most economical and effective measure to control diseases. Altering the susceptibility genes that promote pathogen compatibility via CRISPR/Cas9-mediated gene editing technology has become a new strategy for developing disease-resistant wheat varieties. Calcineurin B-like protein (CBL)-interacting protein kinases (CIPKs) has been demonstrated to be involved in defence responses during plant-pathogen interactions. However, whether wheat CIPK functions as susceptibility factor is still unclear. Here, we isolated a CIPK homoeologue gene TaCIPK14 from wheat. Knockdown of TaCIPK14 significantly increased wheat resistance to Pst, whereas overexpression of TaCIPK14 resulted in enhanced wheat susceptibility to Pst by decreasing different aspects of the defence response, including accumulation of ROS and expression of pathogenesis-relative genes. We generated wheat Tacipk14 mutant plants by simultaneous modification of the three homoeologues of wheat TaCIPK14 via CRISPR/Cas9 technology. The Tacipk14 mutant lines expressed race-nonspecific (RNS) broad-spectrum resistance (BSR) to Pst. Moreover, no significant difference was found in agronomic yield traits between Tacipk14 mutant plants and Fielder control plants under greenhouse and field conditions. These results demonstrate that TaCIPK14 acts as an important susceptibility factor in wheat response to Pst, and knockout of TaCIPK14 represents a powerful strategy for generating new disease-resistant wheat varieties with BSR to Pst.

Topological laser with higher-order corner states in the 2-dimensional Su-Schrieffer-Heeger model.

A nonlinear non-Hermitian topological laser system based on the higher-order corner states of the 2-dimensional (2D) Su-Schrieffer-Heeger (SSH) model is investigated. The topological property of this nonlinear non-Hermitian system described by the quench dynamics is in accordance with that of a normal 2D SSH model. In the topological phase, all sites belonging to the topological corner states begin to emit stable laser light when a pulse is given to any one site of the lattice, while no laser light is emitted when the lattice is in the trivial phase. Furthermore, the next-nearest-neighbor (NNN) couplings are introduced into the strong-coupling unit cells of the 2D SSH model, which open a band gap in the continuous band structure. In the topological phase, similar to the case of 2D SSH model without NNN couplings, the corner sites can emit stable laser light due to the robustness of the higher-order corner states when the NNN couplings are regarded as the perturbation. However, amplitude of the stimulated site does not decay to zero in the trivial phase, because the existence of the NNN couplings in the strong-coupling unit cells make the lattice like one in the tetramer limit, and a weaker laser light is emitted by each corner.

Influence of a topological artificial atom chain on the transmission properties of a cavity.

We explore the influence of the artificial atomic chain on the input-output relation of the cavity. Specifically, we extend the atom chain to the one-dimensional Su-Schrieffer-Heeger (SSH) chain to check the role of atomic topological non-trivial edge state on the transmission characteristics of the cavity. The superconducting circuits can realize the artificial atomic chain. Our results show that the atom chain is not equivalent to atom gas, and the transmission properties of the cavity containing the atom chain are entirely different from that of the cavity containing atom gas. When the atom chain is arranged in the form of topological non-trivial SSH model, the atom chain can be equivalent to the three-level atom, in which the edge state contributes to the second level and is resonant with the cavity, while the high-energy bulk state contributes to form the third level and is greatly detuned with the cavity. Therefore, the transmission spectrum shows no more than three peaks. This allows us to infer the topological phase of the atomic chain and the coupling strength between the atom and the cavity only from the profile of the transmission spectrum. Our work is helping to understand the role of topology in quantum optics.