Structure-function analysis of barley NLR immune receptor MLA10 reveals its cell compartment specific activity in cell death and disease resistance.

Plant intracellular immune receptors comprise a large number of multi-domain proteins resembling animal NOD-like receptors (NLRs). Plant NLRs typically recognize isolate-specific pathogen-derived effectors, encoded by avirulence (AVR) genes, and trigger defense responses often associated with localized host cell death. The barley MLA gene is polymorphic in nature and encodes NLRs of the coiled-coil (CC)-NB-LRR type that each detects a cognate isolate-specific effector of the barley powdery mildew fungus. We report the systematic analyses of MLA10 activity in disease resistance and cell death signaling in barley and Nicotiana benthamiana. MLA10 CC domain-triggered cell death is regulated by highly conserved motifs in the CC and the NB-ARC domains and by the C-terminal LRR of the receptor. Enforced MLA10 subcellular localization, by tagging with a nuclear localization sequence (NLS) or a nuclear export sequence (NES), shows that MLA10 activity in cell death signaling is suppressed in the nucleus but enhanced in the cytoplasm. By contrast, nuclear localized MLA10 is sufficient to mediate disease resistance against powdery mildew fungus. MLA10 retention in the cytoplasm was achieved through attachment of a glucocorticoid receptor hormone-binding domain (GR), by which we reinforced the role of cytoplasmic MLA10 in cell death signaling. Together with our data showing an essential and sufficient nuclear MLA10 activity in disease resistance, this suggests a bifurcation of MLA10-triggered cell death and disease resistance signaling in a compartment-dependent manner.

Supramolecular assembly of Polydopamine@Fe nanoparticles with near-infrared light-accelerated cascade catalysis applied for synergistic photothermal-enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) via Fenton-like reaction is greatly attractive owing to its capability to generate highly cytotoxic •OH radicals from tumoral hydrogen peroxide (H2O2). However, the antitumor efficacy of CDT is often challenged by the relatively low radical generation efficiency and the high levels of antioxidative glutathione (GSH) in tumor microenvironment. Herein, an innovative photothermal Fenton-like catalyst, Fe-chelated polydopamine (PDA@Fe) nanoparticle, with excellent GSH-depleting capability is constructed via one-step molecular assembly strategy for dual-modal imaging-guided synergetic photothermal-enhanced chemodynamic therapy. Fe(III) ions in PDA@Fe nanoparticles can consume the GSH overexpressed in tumor microenvironment to avoid the potential •OH consumption, while the as-produced Fe(II) ions subsequently convert tumoral H2O2 into cytotoxic •OH radicals through the Fenton reaction. Notably, PDA@Fe nanoparticles demonstrate excellent near-infrared light absorption that results in superior photothermal conversion ability, which further boosts above-mentioned cascade catalysis to yield more •OH radicals for enhanced CDT. Taken together with T1-weighted magnetic resonance imaging (MRI) contrast enhancement (r1 = 8.13 mM-1 s-1) and strong photoacoustic (PA) imaging signal of PDA@Fe nanoparticles, this design finally realizes the synergistic photothermal-chemodynamic therapy. Overall, this work offers a new promising paradigm to effectively accommodate both imaging and therapy functions in one well-defined framework for personalized precision disease treatment.

Cu-chelated polydopamine nanozymes with laccase-like activity for photothermal catalytic degradation of dyes.

The industrial applications of enzymes are usually hindered by the high production cost, intricate reusability, and low stability in terms of thermal, pH, salt, and storage. Therefore, the de novo design of nanozymes that possess the enzyme mimicking biocatalytic functions sheds new light on this field. Here, we propose a facile one-pot synthesis approach to construct Cu-chelated polydopamine nanozymes (PDA-Cu NPs) that can not only catalyze the chromogenic reaction of 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AP), but also present enhanced photothermal catalytic degradation for typical textile dyes. Compared with natural laccase, the designed mimic has higher affinity to the substrate of 2,4-DP with Km of 0.13 mM. Interestingly, PDA-Cu nanoparticles are stable under extreme conditions (temperature, ionic strength, storage), are reusable for 6 cycles with 97 % activity, and exhibit superior substrate universality. Furthermore, PDA-Cu nanozymes show a remarkable acceleration of the catalytic degradation of dyes, malachite green (MG) and methylene blue (MB), under near-infrared (NIR) laser irradiation. These findings offer a promising paradigm on developing novel nanozymes for biomedicine, catalysis, and environmental engineering.

Blood cellular membrane-coated Au/polydopamine nanoparticle-targeted NIR-II antibacterial therapy.

Bacterial infections are the primary causes of infectious diseases in humans. In recent years, the abuse of antibiotics has led to the widespread enhancement of bacterial resistance. Concerns have been raised about the identification of a common treatment platform for bacterial infections. In this study, a composite nanomaterial was used for near-infrared II (NIR-II) photothermal antibacterial treatment. Red blood cell membrane was peeled and coated onto the surface of the Au/polydopamine nanoparticle-containing aptamer. The composite nanomaterials based on Au/polydopamine exhibit highest photothermal conversion capability. Moreover, these assembled nanoparticles can quickly enter the body's circular system with a specific capability to recognise bacteria. In vivo experiments demonstrated that the composites could kill bacteria from infected blood while significantly reducing the level of bacteria in various organs. Such assemblies offer a paradigm for the treatment of bacterial infections caused by the side effects of antibiotics.

The power of super-resolution microscopy in modern biomedical science.

Super-resolution microscopy (SRM) technology that breaks the diffraction limit has revolutionized the field of cell biology since its appearance, which enables researchers to visualize cellular structures with nanometric resolution, multiple colors and single-molecule sensitivity. With the flourishing development of hardware and the availability of novel fluorescent probes, the impact of SRM has already gone beyond cell biology and extended to nanomedicine, material science and nanotechnology, and remarkably boosted important breakthroughs in these fields. In this review, we will mainly highlight the power of SRM in modern biomedical science, discussing how these SRM techniques revolutionize the way we understand cell structures, biomaterials assembly and how assembled biomaterials interact with cellular organelles, and finally their promotion to the clinical pre-diagnosis. Moreover, we also provide an outlook on the current technical challenges and future improvement direction of SRM. We hope this review can provide useful information, inspire new ideas and propel the development both from the perspective of SRM techniques and from the perspective of SRM's applications.

NIR-II-triggered photothermal therapy with Au@PDA/PEG-PI for targeted downregulation of PSMA in prostate cancer.

Although positron emission tomography (PET) imaging products targeting prostate-specific membrane antigen (PSMA) have been approved for marketing, clinical challenges remain in the study of its use as a therapeutic target, such as the complex synthesis process and side effects after treatment. Here, we developed a strategy for targeted photothermal therapy (PTT) using PSMA as the target. The results of molecular docking demonstrated that the synthesized PEG modified urea-based PSMA inhibitor (small molecular PSMA inhibitor, PI) PI-PEG has a high affinity energy (binding energy = - 8.3 kcal mol-1) for the PSMA target. Therefore, modification of PI-PEG onto the surface of gold@polydopamine (Au@PDA) with NIR-II absorption could enable targeted PTT against PSMA. This work revealed that the prepared Au@PDA/PEG-PI were not only highly selective for PSMA, but also could efficiently ablate PSMA expression by targeted PTT at the maximum permissible exposure (MPE) of the NIR-II laser. Moreover, Au@PDA/PEG-PI also have potential for photoacoustic (PA) imaging and computed tomography (CT) imaging. As the first strategy to downregulate the expression of PSMA and successfully inhibit prostate cancer by targeted PTT, this study case provides a new idea for the clinical translation of PSMA as an integrated target for tumor diagnosis and anti-tumor treatment. STATEMENT OF SIGNIFICANCE: (1) Au@PDA/PEG-PI NPs were the novel PTT agent to target PSMA and successfully down-regulate PSMA expression. (2) Molecular docking results demonstrated that PI-PEG inhibitors have a high affinity energy for PSMA (binding energy = - 8.3 kcal mol-1). (3) Au@PDA/PEG-PI NPs can be targeted for efficient PTT at the MPE of the NIR-II laser. (4) Au@PDA/PEG-PI NPs also have the potential for PA and CT imaging.

A Dual Heat Shock Protein Down-Regulation Strategy Using PDA/Cu/ICG/R Controlled by NIR "Switch" Enhances Mild-Photothermal Therapy Effect.

The purpose of this study is to down-regulate heat shock proteins and improve the mild photothermal therapy (mild-PTT) effect of polydopamine (PDA) by preparing the nanosystem of Cu2+ and indocyanine green (ICG)-loaded PDA nanospheres with surface modification of integrin-targeted cyclic peptide (cRGD) (PDA/Cu/ICG/R), which can limit ATP synthesis through the double mitochondrial destruction pathway. In vitro and in vivo experiments using PDA/Cu/ICG/R irradiated with an NIR laser demonstrate that when NIR is "OFF," Cu2+ can undergo Fenton-like reaction in tumor cells, producing a large amount of hydroxyl radicals (·OH), which leads to oxidative stress in cells. This oxidative stress can cause mitochondrial oxidative phosphorylation dysfunction, resulting in limited ATP synthesis. When NIR is "ON," mild-PTT can accelerate Cu2+ to produce ·OH. Simultaneously, NIR can activate ICG to produce reactive oxygen species (ROS) storm, amplify intracellular oxidative stress, and continuously damage mitochondria. The biodegradability of PDA greatly reduces the risk of toxicity caused by long-term retention of PDA/Cu/ICG/R in organisms. Finally, the improvement of the mild-PTT effect of PDA is successfully achieved through the double mitochondrial destruction pathway of Cu2+ and ICG controlled by NIR "switch."

Multifunction in One Nanoparticle for Anticancer Therapy: Bowl-Shaped Au@PDA Yolk-Shell NPs.

Multifunctional nanoparticles (NPs) with simultaneous multimodal therapeutic and imaging capabilities are very necessary for biomedical applications. We successfully prepared bowl-shaped gold@polydopamine yolk-shell NPs (bowl-shaped Au@PDA YNPs) by a novel and facile method. The unique bowl-like structure enables a drug loading rate of 92% (920 µg mg-1). The bowl-shaped Au@PDA YNPs are biocompatible, have good photothermal conversion and strong near-infrared (NIR) absorption, and can control drug release under pH/NIR dual response. Bowl-shaped Au@PDA YNPs can also be employed as contrast agents for computed tomography/photoacoustic imaging for dual-modal imaging-guided chemotherapy and photothermal therapy due to the presence of Au NPs.

Formation of α clusters in dilute neutron-rich matter.

The surface of neutron-rich heavy nuclei, with a neutron skin created by excess neutrons, provides an important terrestrial model system to study dilute neutron-rich matter. By using quasi-free α cluster-knockout reactions, we obtained direct experimental evidence for the formation of α clusters at the surface of neutron-rich tin isotopes. The observed monotonous decrease of the reaction cross sections with increasing mass number, in excellent agreement with the theoretical prediction, implies a tight interplay between α-cluster formation and the neutron skin. This result, in turn, calls for a revision of the correlation between the neutron-skin thickness and the density dependence of the symmetry energy, which is essential for understanding neutron stars. Our result also provides a natural explanation for the origin of α particles in α decay.

Molecular analysis of phosphomannomutase (PMM) genes reveals a unique PMM duplication event in diverse Triticeae species and the main PMM isozymes in bread wheat tissues.

BACKGROUND: Phosphomannomutase (PMM) is an essential enzyme in eukaryotes. However, little is known about PMM gene and function in crop plants. Here, we report molecular evolutionary and biochemical analysis of PMM genes in bread wheat and related Triticeae species. RESULTS: Two sets of homologous PMM genes (TaPMM-1 and 2) were found in bread wheat, and two corresponding PMM genes were identified in the diploid progenitors of bread wheat and many other diploid Triticeae species. The duplication event yielding PMM-1 and 2 occurred before the radiation of diploid Triticeae genomes. The PMM gene family in wheat and relatives may evolve largely under purifying selection. Among the six TaPMM genes, the transcript levels of PMM-1 members were comparatively high and their recombinant proteins were all enzymatically active. However, PMM-2 homologs exhibited lower transcript levels, two of which were also inactive. TaPMM-A1, B1 and D1 were probably the main active isozymes in bread wheat tissues. The three isozymes differed from their counterparts in barley and Brachypodium distachyon in being more tolerant to elevated test temperatures. CONCLUSION: Our work identified the genes encoding PMM isozymes in bread wheat and relatives, uncovered a unique PMM duplication event in diverse Triticeae species, and revealed the main active PMM isozymes in bread wheat tissues. The knowledge obtained here improves the understanding of PMM evolution in eukaryotic organisms, and may facilitate further investigations of PMM function in the temperature adaptability of bread wheat.

Retrospective and perspective of rice breeding in China.

Breeding is the art and science of selecting and changing crop traits for the benefit of human beings. For several decades, tremendous efforts have been made by Chinese scientists in rice breeding in improving grain yield, nutrition quality, and environmental performance, achieving substantial progress for global food security. Several generations of crop breeding technologies have been developed, for example, selection of better performance in the field among variants (conventional breeding), application of molecular markers for precise selection (molecular marker assisted breeding), and development of molecular design (molecular breeding by rational design). In this review, we briefly summarize the advances in conventional breeding, functional genomics for genes and networks in rice that regulate important agronomic traits, and molecular breeding in China with focuses on high yield, good quality, stress tolerance, and high nutrient-use efficiency. These findings have paved a new avenue for rational design of crops to develop ideal varieties with super performance and productivity.