In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

The first two whole mitochondrial genomes for the genus Dactylis species: assembly and comparative genomics analysis.

BACKGROUND: Orchardgrass (Dactylis glomerata L.), a perennial forage, has the advantages of rich leaves, high yield, and good quality and is one of the most significant forage for grassland animal husbandry and ecological management in southwest China. Mitochondrial (mt) genome is one of the major genetic systems in plants. Studying the mt genome of the genus Dactylis could provide more genetic information in addition to the nuclear genome project of the genus. RESULTS: In this study, we sequenced and assembled two mitochondrial genomes of Dactylis species of D. glomerata (597, 281 bp) and D. aschersoniana (613, 769 bp), based on a combination of PacBio and Illumina. The gene content in the mitochondrial genome of D. aschersoniana is almost identical to the mitochondrial genome of D. glomerata, which contains 22-23 protein-coding genes (PCGs), 8 ribosomal RNAs (rRNAs) and 30 transfer RNAs (tRNAs), while D. glomerata lacks the gene encoding the Ribosomal protein (rps1) and D. aschersoniana contains one pseudo gene (atp8). Twenty-three introns were found among eight of the 30 protein-coding genes, and introns of three genes (nad 1, nad2, and nad5) were trans-spliced in Dactylis aschersoniana. Further, our mitochondrial genome characteristics investigation of the genus Dactylis included codon usage, sequences repeats, RNA editing and selective pressure. The results showed that a large number of short repetitive sequences existed in the mitochondrial genome of D. aschersoniana, the size variation of two mitochondrial genomes is due largely to the presence of a large number of short repetitive sequences. We also identified 52-53 large fragments that were transferred from the chloroplast genome to the mitochondrial genome, and found that the similarity was more than 70%. ML and BI methods used in phylogenetic analysis revealed that the evolutionary status of the genus Dactylis. CONCLUSIONS: Thus, this study reveals the significant rearrangements in the mt genomes of Pooideae species. The sequenced Dactylis mt genome can provide more genetic information and improve our evolutionary understanding of the mt genomes of gramineous plants.

Application of gold nanoclusters in fluorescence sensing and biological detection.

Gold nanoclusters (Au NCs) exhibit broad fluorescent spectra from visible to near-infrared regions and good enzyme-mimicking catalytic activities. Combined with excellent stability and exceptional biocompatibility, the Au NCs have been widely exploited in biomedicine such as biocatalysis and bioimaging. Especially, the long fluorescence lifetime and large Stokes shift attribute Au NCs to good probes for fluorescence sensing and biological detection. In this review, we systematically summarized the molecular structure and fluorescence properties of Au NCs and highlighted the advances in fluorescence sensing and biological detection. The Au NCs display high sensitivity and specificity in detecting iodine ions, metal ions, and reactive oxygen species, as well as certain diseases based on the fluorescence activities of Au NCs. We also proposed several points to improve the practicability and accelerate the clinical translation of the Au NCs.

Self-Assembled Tetraphenylethene-Based Nanoaggregates with Tunable Electrochemiluminescence for the Ultrasensitive Detection of E. coli.

As an effective ECL emitter, tetraphenylethene (TPE)-based molecules have recently been reported with aggregation-induced electrochemiluminescence (AIECL) property, while it is still a big challenge to control its aggregation states and obtain uniform aggregates with intense ECL emission. In this study, we develop three TPE derivatives carrying a pyridinium group, an alkyl chain, and a quaternary ammonium group via the Menschutkin reaction. The resulting molecules exhibit significantly red-shifted FL and enhanced ECL emissions due to the tunable reduction of the energy gap between the highest occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals (LUMOs). More importantly, the amphiphilicity of the as-developed molecules enables their spontaneous self-assembly into well-controlled spherical nanoaggregates, and the ECL intensity of nanoaggregates with 3 -CH2- (named as C3) is 17.0-fold higher compared to that of the original 4-(4-(1,2,2-triphenylvinyl)phenyl)pyridine (TPP) molecule. These cationic nanoaggregates demonstrate a high affinity toward bacteria, and an ECL sensor for the profiling of Escherichia coli (E. coli) was developed with a broad linear range and good selectivity in the presence of an E. coli-specific aptamer. This study provides an effective way to enhance the ECL emission of TPE molecules through their derivatization and a simple way to prepare well-controlled AIECL nanoaggregates for ECL application.

Bioactive NIR-II gold clusters for three-dimensional imaging and acute inflammation inhibition.

Strong fluorescence and high catalytic activities cannot be achieved simultaneously due to conflicts in free electron utilization, resulting in a lack of bioactivity of most near-infrared-II (NIR-II) fluorophores. To circumvent this challenge, we developed atomically precise Au22 clusters with strong NIR-II fluorescence ranging from 950 to 1300 nm exhibiting potent enzyme-mimetic activities through atomic engineering to create active Cu single-atom sites. The developed Au21Cu1 clusters show 18-fold higher antioxidant, 90-fold higher catalase-like, and 3-fold higher superoxide dismutase-like activities than Au22 clusters, with negligible fluorescence loss. Doping with single Cu atoms decreases the bandgap from 1.33 to 1.28 eV by predominant contributions from Cu d states, and Cu with lost electron states effectuates high catalytic activities. The renal clearable clusters can monitor cisplatin-induced renal injury in the 20- to 120-minute window and visualize it in three dimensions using NIR-II light-sheet microscopy. Furthermore, the clusters inhibit oxidative stress and inflammation in the cisplatin-treated mouse model, particularly in the kidneys and brain.

Long-term application of nitrogen and phosphorus fertilizers changes the process of community construction by affecting keystone species of crop rhizosphere microorganisms.

Keystone species of microbial communities play a very important role in community structure and ecosystem function; however, the effect of long-term nitrogen (N) and phosphorus (P) fertilizers on key taxa and the mechanisms of community construction of rhizosphere microbial communities remain unclear. In this study, the effect of nine fertilization treatments (N0P0, N0P1, N0P2, N1P0, N1P1, N1P2, N2P0, N2P1, and N2P2) on soil microbial community diversity, keystone species, and construction methods in the crop rhizosphere were studied in a loess hilly area after 26 years of fertilization. The results showed that fertilization significantly increased the nutrient contents of the rhizospheric soil and root system and significantly affected microbial community composition (based on the Bray-Curtis distance) and community construction process (ß-nearest taxon index: ßNTI). The decrease in the abundance of oligotrophic bacteria (from phyla Acidobacteriota and Chloroflexi) in the keystone species of bacterial communities shifted the community construction process from homogenizing dispersal to variable selection process and was significantly regulated by soil factors (total P and carbon-N ratio). However, the decrease in the abundance of keystone species (from phylum Basidiomycota) in the fungal communities did not have a significant effect on community construction, which was mainly affected by root characteristics (root N content and soluble sugar). This study found that long-term N and P fertilization changed the keystone species composition of bacterial communities by affecting the nutrient content of the rhizospheric soil, such as total P, so that the construction mode of communities changed from a stochastic to a deterministic process, and the N2 fertilization, especially the N1P2 treatment was better for increasing network stability (modularity and clustering coefficient).

Tracking tumor heterogeneity and progression with near-infrared II fluorophores.

Heterogeneous cells are the main feature of tumors with unique genetic and phenotypic characteristics, which can stimulate differentially the progression, metastasis, and drug resistance. Importantly, heterogeneity is pervasive in human malignant tumors, and identification of the degree of tumor heterogeneity in individual tumors and progression is a critical task for tumor treatment. However, current medical tests cannot meet these needs; in particular, the need for noninvasive visualization of single-cell heterogeneity. Near-infrared II (NIR-II, 1000-1700 nm) imaging exhibits an exciting prospect for non-invasive monitoring due to the high temporal-spatial resolution. More importantly, NIR-II imaging displays more extended tissue penetration depths and reduced tissue backgrounds because of the significantly lower photon scattering and tissue autofluorescence than traditional the near-infrared I (NIR-I) imaging. In this review, we summarize systematically the advances made in NIR-II in tumor imaging, especially in the detection of tumor heterogeneity and progression as well as in tumor treatment. As a non-invasive visual inspection modality, NIR-II imaging shows promising prospects for understanding the differences in tumor heterogeneity and progression and is envisioned to have the potential to be used clinically.

Evolution of antimicrobial cysteine-rich peptides in plants.

KEY MESSAGE: We analyzed the evolutionary pattern of cysteine-rich peptides (CRPs) to infer the relationship between CRP copy number and plant ecotype, and the origin of bi-domains CRPs. Plants produce cysteine-rich peptides (CRPs) that have long-lasting broad-spectrum antimicrobial activity to protect themselves from various groups of pathogens. We analyzed 240 plant genomes, ranging from algae to eudicots, and discovered that CRPs are widely distributed in plants. Our comparative genomics results revealed that CRP genes have been amplified through both whole genome and local tandem duplication. The copy number of these genes varied significantly across lineages and was associated with the plant ecotype. This may be due to their resistance to changing pathogenic environments. The conserved and lineage-specific CRP families contribute to diverse antimicrobial activities. Furthermore, we investigated the unique bi-domain CRPs that result from unequal crossover events. Our findings provide a unique evolutionary perspective on CRPs and insights into their antimicrobial and symbiosis characteristics.

Hyper non-CG methylation of expanded plant disease resistance NLR genes.

KEY MESSAGE: We explored the phylogenomics and methylomics of NLR genes in 41 plant species and found that highly duplicated plant NLR genes are hyper methylated in non-CG context.

Single Atom-Engineered NIR-II Gold Clusters with Ultrahigh Brightness and Stability for Acute Kidney Injury.

Near-infrared-II (NIR-II) imaging has shown great potential for monitoring the pathological progression and deep tissue imaging but is limited to present unmet NIR-II agent. Present fluorophores show a promising prospect for NIR-II imaging, but brightness and photostability are still highly challenging during real-time monitoring. In this work, atom-engineered NIR-II Au24 Cd1  clusters with ultrahigh brightness, stability, and photostability are developed via single atomic Cd doping. Single atom Cd substitutions contribute to Cd 4d state in HOMO and redistribution of energy level near the gap, exhibiting 56-fold fluorescence enhancement of Au24 Cd1  clusters. Meanwhile, single atomic Cd reinforces CdAu bond energy, formation energy, and stabilized cluster structure, leading to persistent stability for up to 1 month without decay, as well as excellent photostability of 1 h without photobleaching, much longer than clinically approved indocyanine green (<5 min). In vivo imaging shows gold clusters can monitor acute kidney injury (AKI) even after 72 h of injury, enabling evaluating progression at a very long window. Meanwhile, the bioactive gold clusters can alleviate AKI-induced oxidative stress damage and acute neuroinflammation. Single atom-engineered gold clusters exhibit molecular tracking and diagnostic prospect in kidney-related diseases.

Catalytic nanotechnology of X-ray photodynamics for cancer treatments.

Photodynamic therapy (PDT) has been applied in cancer treatment because of its high selectivity, low toxicity, and non-invasiveness. However, the limited penetration depth of the light still hampers from reaching deep-seated tumors. Considering the penetrating ability of high-energy radiotherapy, X-ray-induced photodynamic therapy (X-PDT) has evolved as an alternative to overcome tissue blocks. As the basic principle of X-PDT, X-rays stimulate the nanoparticles to emit scintillating or persistent luminescence and further activate the photosensitizers to generate reactive oxygen species (ROS), which would cause a series of molecular and cellular damages, immune response, and eventually break down the tumor tissue. In recent years, catalytic nanosystems with unique structures and functions have emerged that can enhance X-PDT therapeutic effects via an immune response. The anti-cancer effect of X-PDT is closely related to the following factors: energy conversion efficiency of the material, the radiation dose of X-rays, quantum yield of the material, tumor resistance, and biocompatibility. Based on the latest research in this field and the classical theories of nanoscience, this paper systematically elucidates the current development of the X-PDT and related immunotherapy, and highlights its broad prospects in medical applications, discussing the connection between fundamental science and clinical translation.

Intelligent Optimization Method of Resource Recommendation Service of Mobile Library Based on Digital Twin Technology.

In order to improve the Resource Recommendation and sharing ability of mobile library, an intelligent optimization model of Mobile Library Resource Recommendation Service Based on digital twin technology is proposed. Build the association rule feature distribution set of mobile library resource recommendation service, carry out text information retrieval in the process of Mobile Library Resource Recommendation and sharing, carry out semantic correlation feature registration according to the retrieval preference of mobile library reading user object, establish the association rule data set of mobile library reading user object preference for mobile library Resource Recommendation and sharing, carry out feature block processing, and analyze the library reader preference. Complete the collaborative filtering recommendation of Mobile Library Resource Recommendation sharing. The simulation results show that the collaborative recommendation under the intelligent optimization mode of mobile library resource recommendation service using this method has high accuracy and good confidence level, which improves the intelligent level of Mobile Library Resource Recommendation and user satisfaction.

Single-atom nanozymes catalytically surpassing naturally occurring enzymes as sustained stitching for brain trauma.

Regenerable nanozymes with high catalytic stability and sustainability are promising substitutes for naturally-occurring enzymes but are limited by insufficient and non-selective catalytic activities. Herein, we developed single-atom nanozymes of RhN4, VN4, and Fe-Cu-N6 with catalytic activities surpassing natural enzymes. Notably, Rh/VN4 preferably forms an Rh/V-O-N4 active center to decrease reaction energy barriers and mediates a "two-sided oxygen-linked" reaction path, showing 4 and 5-fold higher affinities in peroxidase-like activity than the FeN4 and natural horseradish peroxidase. Furthermore, RhN4 presents a 20-fold improved affinity in the catalase-like activity compared to the natural catalase; Fe-Cu-N6 displays selectivity towards the superoxide dismutase-like activity; VN4 favors a 7-fold higher glutathione peroxidase-like activity than the natural glutathione peroxidase. Bioactive sutures with Rh/VN4 show recyclable catalytic features without apparent decay in 1 month and accelerate the scalp healing from brain trauma by promoting the vascular endothelial growth factor, regulating the immune cells like macrophages, and diminishing inflammation.

Nanozyme-natural enzymes cascade catalyze cholesterol consumption and reverse cancer multidrug resistance.

Multidrug resistance is still a major obstacle to cancer treatment. The most studies are to inhibit the activity of the drug transporter P-glycoprotein (P-gp), but the effect is not ideal. Herein, a nanosystem was built based on cascade catalytic consumption of cholesterol. Cholesterol oxidase (natural enzyme, COD) was immobilized on the carrier (NH2-MIL-88B, MOF) through amide reaction, COD catalyzed the consumption of cholesterol, the reaction product H2O2 was further produced by the MOF with its peroxidase-like activity to produce hydroxyl radicals (•OH) with killing effect. Due to the high expression of CD44 receptor on the surface of tumor cells, we encapsulated chondroitin sulfate gel shell (CS-shell) with CD44 targeting and apoptosis promoting effect on the surface of DOX@MOF-COD nanoparticles, which can accurately and efficiently deliver the drugs to the tumor site and improve the effect of reversing drug resistance. Taking drug-resistant cell membrane as "breakthrough", this paper will provide a new idea for reversing multidrug resistance of tumor.

Activatable NIR-II organic fluorescent probes for bioimaging.

NIR-II imaging is developed rapidly for noninvasive deep tissue inspection with high spatio-temporal resolution, taking advantage of diminished autofluorescence and light attenuation. Activatable NIR-II fluorescence probes are widely developed to report pathological changes with accurate targeting, among which organic fluorescent probes achieve significant progress. Furthermore, the activatable NIR-II fluorescent probes exhibited appealing characteristics like tunable physicochemical and optical properties, easy processability, and excellent biocompatibility. In the present review, we highlight the advances of activatable NIR-II fluorescence probes in design, synthesis and applications for imaging pathological changes like reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), pH, hypoxia, viscosity as well as abnormally expressed enzymes. This non-invasive optical imaging modality shows a promising prospect in targeting the pathological site and is envisioned for potential clinical translation.

Glutamine Metabolism-Regulated Nanoparticles to Enhance Chemoimmunotherapy by Increasing Antigen Presentation Efficiency.

Although the strategies to induce dendritic cells (DCs) maturation and promote their antigen presentation can stimulate the tumor immune response, the endogenous deficiency and immunosuppression of DCs reduce antigen utilization, which limits antigen presentation efficiency and reduces immunotherapy effectiveness. Here, we report an endogenous stimulus-responsive nanodelivery system (DOX@HFn-MSO@PGZL). On the one hand, doxorubicin (DOX) promoted antigen presentation by DCs after the immunogenic death of tumor cells. On the other hand, l-methionine sulfoximine (MSO) regulated the glutamine metabolism of tumor-associated macrophages (TAMs) to induce a shift toward the M1-type. M1-TAMs synergistically presented antigens with mature DCs and were more frequently produced to destroy the tumor suppressive immune microenvironment, resulting in the alleviation of DCs functional inhibition. Ultimately, the antigen presentation efficiency was improved, completely activating tumor immunity and exhibiting powerful antitumor effects.

Effects of college students' mindfulness on depression symptoms during the epidemic prevention and control period: The mediating effect of psychological resilience.

Depression symptoms significantly impact college students' mental health, particularly during the "closed management" period during the spread of COVID-19. Exploring the mechanism that affects college students' depression symptoms can help alleviate the impact of closed management policies on individual mental health and improve their mental health level. The onset of the COVID-19 pandemic resulted in the normalization of epidemic prevention and control in China and the implementation of the dynamic zero-COVID policy. This study used the Five-Factor Mindfulness Questionnaire-Short Form, Psychological Resilience Scale, and Beck Depression Scale to investigate the mindfulness, psychological resilience, and depression symptoms of 1,062 students under closed management conditions at Northwest Normal University. The mindfulness, psychological resilience, and depression status of students in closed management were investigated using an online questionnaire survey. Eight hundred and ten college students (M age = 20.43, SD = 1.67, range = 17-30) were selected to test the model using the structural equation model and bootstrap method. The results showed that the gender differences in mindfulness and psychological resilience were not significant. Gender differences in depression symptoms were significant, and depression symptoms in men were significantly higher than in women. Grade differences in resilience, mindfulness, and depression levels were not significant. Thus, psychological resilience is negatively associated with depressive symptoms. Psychological resilience plays a mediating role between mindfulness and depressive symptoms. This study provides reference and inspiration for improving college students' mental health under epidemic prevention and control circumstances.

Quality characteristics of semi-glutinous japonica rice cultivated in the middle and lower reaches of the Yangtze River in China.

BACKGROUND: Semi-glutinous japonica rice (SGJR) is increasingly a popular choice for rice consumption and more commonly cultivated in the middle and lower reaches of the Yangtze River in China. Here, 58 SGJR and 75 non-semi-glutinous japonica rice (NSGJR) cultivars were evaluated for their characteristics of grain quality by assessing the taste of cooked grains, flour/paste properties, chemical compositions and starch physicochemical properties. RESULTS: Comparisons of factors related to taste showed that cooked rice characteristics of SGJR were better in appearance, lower in hardness, lower in springiness and higher in stickiness. There were no significant differences in contents of total starch and total protein between the two types of rice. Further analysis indicates that thinner lamellar thickness, smaller starch particle size, and higher contents of amylopectin and albumin of SGJR (resulting in higher weights of dried matter from rice slurries) contributed to better appearance of cooked SGJR. Lower contents of amylose and prolamin led to a weaker and less elastic gel network in rice paste samples and contributed to a stronger moisture migration capability of cooked SGJR that showed higher stickiness and lower hardness and springiness. CONCLUSION: A SGJR line with low apparent amylose content does not indicate good taste. Physicochemical properties of starch and protein contributed to better appearance, higher stickiness and lower hardness and springiness of cooked SGJR. These findings provide empirical data to help breed better-tasting cultivars of japonica rice. © 2021 Society of Chemical Industry.

Ligand-Modulated Catalytic Selectivity of Ag Clusterzyme for Relieving Multiorgan Injury via Inhabiting Acute Oxidative Stress.

The artificial enzymes at the atomic level have shown great potential in chemical biology and nanomedicine, and modulation of catalytic selectivity is also critical to the application of nanozymes. In this work, atomic precision Ag25 clusterzymes protected by single- and dual-ligand were developed. Further, the catalytic activity and selectivity of Ag25 clusterzymes were modulated by adjusting doping elements and ligand. The Ag24Pt1 shows more prominent antioxidant activity characteristics in the dual-ligand system, while the Ag24Cu1 possesses the superoxide dismutase-like (SOD-like) activity regardless of the single- or dual-ligand system, indicating modulated catalytic selectivity. In vitro experiments showed the Ag24Pt1-D can recover radiation induced DNA damages and eliminate the excessive reactive oxygen species (ROS) generated from radiation. Subsequent in vivo radiation protection experiments reveal that Ag24Cu1-S and Ag24Pt1-D can improve the survival rate of irradiated mice from 0 to 40% and 30%, respectively. The detailed biological experiments confirm that the Ag24Cu1-S and Ag24Pt1-D can recover the SOD and 3,4-methylenedioxyamphetamine (MDA) levels via suppressing the chronic inflammation reaction. Nearly 60% of Ag24Cu1-S and Ag24Pt1-D can be excreted after a 1 day injection, and no obvious toxicological reactions were observed 30 days after injection.

Atomic Engineering of Clusterzyme for Relieving Acute Neuroinflammation through Lattice Expansion.

Natural enzymes are efficient and versatile biocatalysts but suffer in their environmental tolerance and catalytic stability. As artificial enzymes, nanozymes can improve the catalytic stability, but it is still a challenge to achieve high catalytic activity. Here, we employed atomic engineering to build the artificial enzyme named Au24Ag1 clusterzyme that hosts an ultrahigh catalytic activity as well as strong physiological stability via atom manipulation. The designed Au24Ag1 clusterzyme activates the Ag-S active site via lattice expansion in the oligomer atom layer, showing an antioxidant property 72 times higher than that of natural antioxidant Trolox. Enzyme-mimicked studies find that Au24Ag1 clusterzyme exhibits high catalase-like (CAT-like) and glutathione peroxidase-like (GPx-like) activity with a maximum reaction rate of 68.9 and 17.8 µM/min, respectively. Meanwhile, the unique catalytic landscape exhibits distinctive reactions against inflammation by inhibiting the cytokines at an early stage in the brain. Atomic engineering of clusterzymes provides a powerful and attractive platform with satisfactory atomic dispersion for tailoring biocatalysts freely at the atomic level.